Publications by authors named "Rui-Xing Yin"

148 Publications

No causal effects of plasma homocysteine levels on the risk of coronary heart disease or acute myocardial infarction: A Mendelian randomization study.

Eur J Prev Cardiol 2021 04 16;28(2):227-234. Epub 2019 Dec 16.

Clinical Laboratory of The Affiliated Cancer Hospital, Guangxi Medical University, China.

Background: Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction.

Methods: A two-sample Mendelian randomization study on disease was conducted, i.e. "coronary heart disease" (n = 184,305) and "acute myocardial infarction" (n = 181,875). Nine single nucleotide polymorphisms, which were genome-wide significantly associated with plasma homocysteine levels in 57,644 subjects from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium genome-wide association study and were known to be associated at p < 5×10-8, were used as an instrumental variable.

Results: None of the nine single nucleotide polymorphisms were associated with coronary heart disease or acute myocardial infarction (p > 0.05 for all). Mendelian randomization analysis revealed no causal effects of plasma homocysteine levels, either on coronary heart disease (inverse variance weighted; odds ratio = 1.015, 95% confidence interval = 0.923-1.106, p = 0.752) or on acute myocardial infarction (inverse variance weighted; odds ratio = 1.037, 95% confidence interval = 0.932-1.142, p = 0.499). The results were consistent in sensitivity analyses using the weighted median and Mendelian randomization-Egger methods, and no directional pleiotropy (p = 0.213 for coronary heart disease and p = 0.343 for acute myocardial infarction) was observed. Sensitivity analyses confirmed that plasma homocysteine levels were not significantly associated with coronary heart disease or acute myocardial infarction.

Conclusions: The findings from this Mendelian randomization study indicate no causal relationship between plasma homocysteine levels and coronary heart disease or acute myocardial infarction. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.
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http://dx.doi.org/10.1177/2047487319894679DOI Listing
April 2021

Associations between SNPs, their haplotypes, gene-gene, and gene-environment interactions and dyslipidemia.

Aging (Albany NY) 2021 02 17;13(4):5906-5927. Epub 2021 Feb 17.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.

In this study, we investigated associations between single nucleotide polymorphisms (SNPs) in the tubulin beta class I () and WW domain-containing oxidoreductase () genes, gene-gene interactions, and gene-environment interactions and dyslipidemia in the Chinese Maonan ethnic group. Four SNPs (rs3132584, rs3130685, rs2222896, and rs2548861) were genotyped in unrelated subjects with normal lipid levels (864) or dyslipidemia (1129). While 5.0% of Maonan subjects carried the rs3132584TT genotype, none of the Chinese Han in Beijing subjects did. Allele and genotype frequencies differed between the normal and dyslipidemia groups for three SNPs (rs3132584, rs3130685, and rs2222896). rs2222896G allele carriers in the normal group had higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol levels. The rs3132584GG, rs3130685CC+TT, and rs2222896GG genotypes as well as the rs2222896G-rs2548861G and rs2222896G-rs2548861T haplotypes were associated with an elevated risk of dyslipidemia; the rs2222896A-rs2548861T and rs2222896A-rs2548861G haplotypes were associated with a reduced risk of dyslipidemia. Among the thirteen interaction types identified, rs3132584T-rs3130685T-rs2222896G-rs2548861T increased the risk of dyslipidemia 1.371-fold. Fourteen two- to four-locus optimal interactive models for SNP-SNP, haplotype-haplotype, gene-gene, and gene-environment interactions exhibited synergistic or contrasting effects on dyslipidemia. Finally, the interaction between rs3132584 and rs2222896 increased the risk of dyslipidemia 2.548-fold and predicted hypertension.
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http://dx.doi.org/10.18632/aging.202514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950260PMC
February 2021

Association between SLC44A4-NOTCH4 SNPs and serum lipid levels in the Chinese Han and Maonan ethnic groups.

Nutr Metab (Lond) 2020 Dec 14;17(1):105. Epub 2020 Dec 14.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China.

Background: The current research was to assess the relationship of the solute carrier family 44 member 4 (SLC44A4) rs577272, notch receptor 4 (NOTCH4) rs3134931 SNPs and serum lipid levels in the Han and Maonan ethnic groups.

Methods: The genetic makeup of the SLC44A4 rs577272 and NOTCH4 rs3134931 SNPs in 2467 unrelated subjects (Han, 1254; Maonan,1213) was obtained by using polymerase chain reaction and restriction fragment length polymorphism technique, combined with gel electrophoresis, and confirmed by direct sequencing.

Results: The genotype frequencies of SLC44A4 rs577272 and NOTCH4 rs3134931 SNPs were different between Han and Maonan populations (P < 0.05); respectively. The SLC44A4 rs577272 SNP was associated with total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels in Maonan group. The NOTCH4 rs3134931 SNP was associated with triglyceride (TG) in Han; and TG and low-density lipoprotein cholesterol (LDL-C) levels in Maonan groups (P < 0.025-0.001). Stratified analysis according to gender showed that the SLC44A4 rs577272 SNP was associated with TC and HDL-C in Han and Maonan females; TC in Maonan males, meanwhile, the NOTCH4 rs3134931 SNP was associated with TG and HDL-C in Han males; TG in Han females; TG and LDL-C in Maonan males; and TG, HDL-C and LDL-C in Maonan females. Linkage disequilibrium analysis showed that the most common haplotype was rs577272G-rs3134931A (> 50%) in both Han and Maonan groups. The haplotype of rs577272G-rs3134931A was associated with TG and HDL-C in Han; and TC, TG and HDL-C in Maonan ethnic groups.

Conclusions: These results suggest that the relationship among SLC44A4 rs577272, NOTCH4 rs3134931 SNPs and serum lipid parameters may vary depending on the gender and/or ethnicity/race in some populations. Haplotypes could explain more changes in serum lipid parameters than any single SNP alone particularly for TC, TG and HDL-C.
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http://dx.doi.org/10.1186/s12986-020-00533-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737288PMC
December 2020

CMIP SNPs and their haplotypes are associated with dyslipidaemia and clinicopathologic features of IgA nephropathy.

Biosci Rep 2020 10;40(10)

Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China.

The relationship between serum lipid profiles and related clinicopathologic features of IgA nephropathy (IgAN) and c-Maf-inducing protein (CMIP) gene polymorphisms is unclear. The present study was designed to examine the effect of CMIP single-nucleotide polymorphisms (SNPs) on dyslipidaemia and clinicopathologic features of IgAN. Clinical and pathological data from patients with IgAN diagnosed at the First Affiliated Hospital of Guangxi Medical University were collected. DNA was extracted from blood samples. CMIP rs2925979 and CMIP rs16955379 genotypes were determined by PCR and direct sequencing. Among 543 patients, 281 had dyslipidaemia (51.7%). Compared with the non-dyslipidaemia group, the dyslipidaemia group exhibited higher blood pressure, blood urea nitrogen, uric acid, and body mass index; higher prevalence of oedema, haematuria, tubular atrophy, and interstitial fibrosis; and lower albumin and estimated glomerular filtration rate. In the dyslipidaemia group, the frequency of C allele carriers was higher than that of non-C allele carriers for rs16955379. Multivariate linear regression analysis showed that total cholesterol, low-density lipoprotein and high-density lipoprotein were associated with rs16955379C allele carriers. Apolipoprotein B was associated with A allele carriers of rs2925979. Linkage disequilibrium was observed between rs16955379 and rs2925979, and rs2925979G-rs16955379T was the most common haplotype. The frequencies of the four CMIP SNP haplotypes differed between dyslipidaemia and non-dyslipidaemia groups in IgAN (P<0.05, for all above). Dyslipidaemia is a common complication in IgAN patients, and those with dyslipidaemia present poor clinicopathologic features. CMIP SNPs and their haplotypes are closely correlated with the occurrence of dyslipidaemia and clinicopathologic damage in IgAN patients.
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http://dx.doi.org/10.1042/BSR20202628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593538PMC
October 2020

Potential Molecular Mechanism of the Gene in Postischemic Heart Failure with and without T2DM.

Biomed Res Int 2020 3;2020:2159460. Epub 2020 Aug 3.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530021 Guangxi, China.

Background: This study is aimed at investigating natriuretic peptide B () coexpression genes and their pathways involved in heart failure (HF) among patients both with and without type 2 diabetes mellitus (T2DM).

Methods: The microarray dataset GSE26887, containing 19 postischemic HF patients' peripheral blood samples (7 with T2DM and 12 without T2DM), was examined to detect the genes coexpressed with using the corr.test function in the R packet. Furthermore, using online analytical tools, we determined the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Gene Ontology (GO) annotation, and protein-protein interaction (PPI) network of the coexpression genes. The modules and hub genes of the PPI network were then identified using the Cytoscape software.

Results: In patients with T2DM, a total of 41 biological processes (BP), 20 cellular components (CC), 13 molecular functions (MF), and 41 pathways were identified. Furthermore, a total of 61 BPs, 16 CCs, 13 MFs, and 22 pathways in patients without T2DM were identified. In both groups of patients, 17 BPs, 10 CCs, 6 MFs, and 13 pathways were enriched. We also identified 173 intersectional coexpression genes (63 positively, 106 negatively, and 4 differently coexpressed in patients with and without T2DM, respectively) in both types of patients, which were enriched in 16 BPs, 8 CCs, 3 MFs, and 8 KEGG pathways. Moreover, the PPI network (containing 237 edges and 170 nodes) with the top module significantly enriched in 4 BPs (tricarboxylic acid metabolic process, citrate metabolic process, tricarboxylic acid cycle, and aerobic respiration) and 3 pathways (citrate cycle, malaria parasite metabolic pathway, and AGE-RAGE signaling pathway in diabetic complications) was constructed. , , , , and are the top hub genes.

Conclusions: Our findings may elucidate the functions and roles of the gene in patients with postischemic HF and facilitate HF management.
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http://dx.doi.org/10.1155/2020/2159460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424400PMC
August 2020

The MC4R SNPs, their haplotypes and gene-environment interactions on the risk of obesity.

Mol Med 2020 08 8;26(1):77. Epub 2020 Aug 8.

Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China.

Background: Little is known about the correlation between the melanocortin 4 receptor gene (MC4R) single nucleotide polymorphisms (SNPs) and the risk of obesity. This research sought to test the MC4R rs17782313, rs476828 and rs12970134 SNPs, their haplotypes and gene-environment interactions on the risk of obesity in the Maonan ethnic group, an isolated minority in China.

Methods: A case-control study comprised of 1836 participants (obesity group, 858; and control group, 978) was conducted. Genotypes of the three SNPs were determined by the next-generation sequencing (NGS) technology.

Results: The genotypic frequencies of the three SNPs were different between the obesity and control groups (P <  0.05 for all). The minor allelic frequency of the MC4R rs17782313C, rs476828C and rs12970134A was higher in obesity than in control groups (13.8% vs. 8.3%, P <  0.001, 17.1% vs. 10.9%, P <  0.001; and 15.5% vs. 11.5%, P <  0.001; respectively). Additionally, the dominant model of rs17782313 and rs476828 SNPs revealed an increased morbidity function on the risk of obesity (P <  0.05). A correlation between SNP-environment and the risk of obesity was also observed. The rs17782313C-rs476828C-rs12970134A haplotype was associated with high risk of obesity (OR = 1.796, 95% CI = 1.447-2.229), whereas the rs17782313T-rs476828T-rs12970134G and rs17782313T-rs476828T-rs12970134A haplotypes were associated with low risk of obesity (OR = 0.699, 95% CI = 0.586-0.834 and OR = 0.620, 95% CI = 0.416-0.925; respectively). The interactions between haplotype and waist circumference on the risk of obesity were also noted.

Conclusions: We discovered that the MC4R rs17782313, rs476828 and rs12970134 SNPs and their haplotypes were associated with the risk of obesity in the Chinese Maonan population.
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http://dx.doi.org/10.1186/s10020-020-00202-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414557PMC
August 2020

Associations of PRKN-PACRG SNPs and G × G and G × E interactions with the risk of hyperlipidaemia.

Sci Rep 2020 08 3;10(1):13010. Epub 2020 Aug 3.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China.

This research aimed to assess the associations of 7 parkin RBR E3 ubiquitin protein ligase (PRKN) and 4 parkin coregulated gene (PACRG) single-nucleotide polymorphisms (SNPs), their haplotypes, gene-gene (G × G) and gene-environment (G × E) interactions with hyperlipidaemia in the Chinese Maonan minority. The genotypes of the 11 SNPs in 912 normal and 736 hyperlipidaemic subjects were detected with next-generation sequencing technology. The genotypic and allelic frequencies of the rs1105056, rs10755582, rs2155510, rs9365344, rs11966842, rs6904305 and rs11966948 SNPs were different between the normal and hyperlipidaemic groups (P < 0.05-0.001). Correlations between the above 7 SNPs and blood lipid levels were also observed (P < 0.0045-0.001, P < 0.0045 was considered statistically significant after Bonferroni correction). Strong linkage disequilibrium was found among the 11 SNPs (r = 0.01-0.64). The most common haplotypes were PRKN C-G-T-G-T-T-C (> 15%) and PACRG A-T-A-T (> 40%). The PRKN C-G-C-A-T-T-C and PRKN-PACRG C-G-T-G-T-T-C-A-T-A-T haplotypes were associated with an increased risk of hyperlipidaemia, whereas the PRKN-PACRG C-G-T-G-C-T-C-A-T-C-T and C-G-T-G-T-T-C-A-T-C-T haplotypes provided a protective effect. Association analysis based on the haplotypes and G × G interaction could improve the power to detect the risk of hyperlipidaemia over the analysis of any one SNP alone. The differences in serum lipid parameters between the hyperlipidaemic and normal groups might partly be due to the effects of the PRKN-PACRG SNPs and their haplotypes.
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http://dx.doi.org/10.1038/s41598-020-68826-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400760PMC
August 2020

Association of the SNPs and gene-gene and gene-environment interactions with serum lipid levels.

Aging (Albany NY) 2020 06 22;12(12):11893-11913. Epub 2020 Jun 22.

Department of Cardiology, Liuzhou People's Hospital, Liuzhou 545006, Guangxi, People's Republic of China.

This study investigated the association of the SNPs and gene-gene and gene-environment interactions with serum lipid levels in the population of Southwest China. Genotyping of 12 SNPs (i.e., rs2238675, rs2228603, rs58542926, rs735273, rs16996148, rs968525, rs17216525, rs12610185, rs10401969, rs8102280, rs73001065 and rs150268548) was performed in 1248 hyperlipidemia patients and 1248 normal subjects. The allelic and genotypic frequencies of the detected SNPs differed substantially between the normal and hyperlipidemia groups ( < 0.05-0.001), and the association of the 12 SNPs and hyperlipidemia was also observed ( < 0.004-0.0001). Four haplotypes (i.e., C-C, G-T, G-C, and C-A-G-T) and 5 gene-gene interaction haplotypes (i.e., rs2238675C-rs2228603C, rs16996148G-rs17216525T, rs12610185G-rs10401969C, rs73001065G-rs8102280A-rs150268548G-rs968525C and rs73001065C-rs8102280A-rs150268548G-rs96852)showed a protective effect, whereas four other haplotypes (i.e., T-A, C-A, G-G-G-C and C-G-A-T), as well as 4 gene-gene interaction haplotypes (i.e., rs58542926C-rs735273A, rs58542926T-rs735273A, rs73001065G-rs8102280G-rs150268548G-rs968525C, and rs73001065C-rs8102280G-rs150268548A-rs968525T), exhibited an inverse effect on hyperlipidemia ( < 0.05-0.0001). There were notable three-locus models comprising SNP-SNP, SNP-environment, and haplotype-haplotype interactions ( < 0.05-0.0001). The individuals with some genotypes and haplotypes reduced the prevalence of hyperlipidemia, whereas the individuals with some other genotypes and haplotypes augmented the prevalence of hyperlipidemia. The SNPs and gene-gene and gene-environment interactions on hyperlipidemia were observed in the population of Southwest China.
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http://dx.doi.org/10.18632/aging.103361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343441PMC
June 2020

SYNE1-QK1 SNPs, G × G and G × E interactions on the risk of hyperlipidaemia.

J Cell Mol Med 2020 05 13;24(10):5772-5785. Epub 2020 Apr 13.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.

This study aimed to assess the relationship of 3 spectrin repeat containing nuclear envelope protein 1 (SYNE1) and 4 KH domain containing RNA binding (QK1) single nucleotide polymorphisms (SNPs), their haplotypes, gene-gene (G × G), gene-environment (G × E) interactions and hypercholesterolaemia (HCH) and hypertriglyceridaemia (HTG) in the Chinese Maonan minority. The genetic make-up of the SYNE1-QK1 SNPs in 1932 unrelated subjects (normal, 641; HCH, 649; and HTG, 642) was obtained by next-generation sequencing technologies. The genotypic frequencies of following SNPs were suggestively distinctive between the control and HCH groups (rs2623963, rs7745725, rs9459317, rs16897566), or between the control and HTG groups (rs2623963, rs1358317, rs7745725, rs1923608, rs16897566 SNPs; P < .05, respectively). Multiple-locus linkage disequilibrium analysis indicated that the identified SNPs were not inherited independently. Several haplotypes and gene-gene interaction haplotypes among the detected SNPs may be related with an increased morbidity of HCH (C-G-A, C-G-G and C-G-G-T-C-A-T) and HTG (C-G-G, G-T-G-C, C-G-G-G-T-G-C and C-G-G-T-C-A-T), whereas others may be related with an decreased risk of HCH (G-A-A, G-C-A-T, C-A-A-T-C-A-T and G-A-A-G-C-A-T) and HTG (G-A-A, G-C-A-T, C-A-A-T-C-A-T and G-A-A-G-C-A-T). The association evaluation based on haplotypes and gene-gene interactions could improve the power of detecting the risk of dyslipidaemia than anyone of SNP alone. There was significant three-locus model involving SNP-SNP, haplotype-haplotype/environment and G × G interactions (P < .05-0.001) that were detected by GMDR in HCH and HTG groups. Different interactions between genetic and environmental factors would produce different redundancy or synergy effects on the morbidity of HCH and/or HTG.
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http://dx.doi.org/10.1111/jcmm.15239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214174PMC
May 2020

SNPs, Their Haplotypes, and Gene-Environment Interactive Effects on Serum Lipid Levels.

ACS Omega 2020 Apr 27;5(13):7158-7169. Epub 2020 Mar 27.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.

The associations between single nucleotide polymorphisms (SNPs) rs2710642 and rs10496099 and their effect on the EH domain-binding protein 1 () gene and serum lipid profiles remain uncertain. This study was performed to investigate the two SNPs in Han and Maonan populations, including their association, haplotypes, and effects on serum lipid levels. Two SNPs in 564 Han and 796 Maonan participants were genotyped by high-throughput sequencing, and then the genotype and haplotype distributions of two SNPs were analyzed. Moreover, risk factors and their effects on serum lipid levels were analyzed using multivariable linear regression and logistic regression analyses. In Han and Maonan populations, a significant difference was found in the allelic and genotypic frequencies of the rs2710642 and rs10496099 SNPs and the alternate alleles of rs2710642A and rs10496099C might be potentially beneficial for healthy lipid levels. Medium linkage disequilibrium between the two SNPs was noted in each ethnic group, and four main haplotypes were detected. The rs2710642G-rs10496099C haplotype was associated with high triglycerides (TGs) and low high-density lipoprotein cholesterol, and the rs2710642A-rs10496099C haplotype was associated with low TGs and high apolipoprotein A1. The rs2710642G-rs10496099C haplotype was a high-risk factor for hyperlipidemia, and it interacted with smoking, fasting blood glucose, and hypertension to increase but with the female factor to decrease the prevalence of hyperlipidemia in Han individuals. The rs2710642 and rs10496099 SNPs and gene-environment interactions were associated with serum lipid profiles and hyperlipidemia, which is of ethnic specificity to our study populations.
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http://dx.doi.org/10.1021/acsomega.9b03522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143410PMC
April 2020

Genes associated with inflammation may serve as biomarkers for the diagnosis of coronary artery disease and ischaemic stroke.

Lipids Health Dis 2020 Mar 12;19(1):37. Epub 2020 Mar 12.

Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.

Background: The current research aimed to expound the genes and pathways that are involved in coronary artery disease (CAD) and ischaemic stroke (IS) and the related mechanisms.

Methods: Two array CAD datasets of (GSE66360 and GSE97320) and an array IS dataset (GSE22255) were downloaded. Differentially expressed genes (DEGs) were identified using the limma package. The online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) (version 6.8; david.abcc.ncifcrf.gov) was used to annotate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses of the DEGs. A protein-protein interaction (PPI) network was constructed by Cytoscape software, and then Molecular Complex Detection (MCODE) analysis was used to screen for hub genes. The hub genes were also confirmed by RT-qPCR and unconditional logistic regression analysis in our CAD and IS patients.

Results: A total of 20 common DEGs (all upregulated) were identified between the CAD/IS and control groups. Eleven molecular functions, 3 cellular components, and 49 biological processes were confirmed by GO enrichment analysis, and the 20 common upregulated DEGs were enriched in 21 KEGG pathways. A PPI network including 24 nodes and 68 edges was constructed with the STRING online tool. After MCODE analysis, the top 5 high degree genes, including Jun proto-oncogene (JUN, degree = 9), C-X-C motif chemokine ligand 8 (CXCL8, degree = 9), tumour necrosis factor (TNF, degree = 9), suppressor of cytokine signalling 3 (SOCS3, degree = 8) and TNF alpha induced protein 3 (TNFAIP3, degree = 8) were noted. RT-qPCR results demonstrated that the expression levels of CXCL8 were increased in IS patients than in normal participants and the expression levels of SOCS3, TNF and TNFAIP were higher in CAD/IS patients than in normal participants. Meanwhile, unconditional logistic regression analysis revealed that the incidence of CAD or IS was positively correlated with the CXCL8, SOCS3, TNF and TNFAIP3.

Conclusions: The CXCL8, TNF, SOCS3 and TNFAIP3 associated with inflammation may serve as biomarkers for the diagnosis of CAD or IS. The possible mechanisms may involve the Toll-like receptor, TNF, NF-kappa B, cytokine-cytokine receptor interactions and the NOD-like receptor signalling pathways.
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http://dx.doi.org/10.1186/s12944-020-01217-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066794PMC
March 2020

rs7014968 SNP Increases Serum Total Cholesterol Levels and the Risk of Coronary Heart Disease and Ischemic Stroke.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620902844

Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Disease Control and Prevention, Nanning, Guangxi, People's Republic of China.

The X Kell blood group complex subunit-related family member 6 () gene single-nucleotide polymorphisms (SNPs) have been associated with serum lipid profiles and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in several previous studies, but the association between the rs7014968 SNP and serum lipid levels and the risk of CHD and IS has not been detected previously. This study aims to explore the association between the rs7014968 SNP and serum lipid traits and the susceptibility to CHD and IS in the Guangxi Han Chinese population. Snapshot technology was used to determine the genotypes of the rs7014968 SNP in 624 controls, 588 patients with CHD, and 544 patients with IS. The rs7014968C allele carriers in the control group had higher serum total cholesterol (TC) levels than the C allele noncarriers ( .025). The rs7014968C allele carriers also had an increased risk of CHD and IS ( < .05-.01). Stratified analysis showed that the patients with the rs7014968C allele in the female, age >60 years, body mass index (BMI) >24 kg/m, and hypertension subgroups had a higher risk of CHD than those in the subgroup counterparts. The patients with the rs7014968C allele in the male, BMI > 24 kg/m, smoker, and hypertension subgroups also had a higher risk of IS than those in the subgroup counterparts. These results suggest that the rs7014968 SNP is likely to increase the risk of CHD and IS by increasing serum TC levels in our study populations.
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http://dx.doi.org/10.1177/1076029620902844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288804PMC
October 2020

Association between the rs634501 polymorphism and serum lipid traits in the Chinese Han and Maonan ethnic groups.

Int J Clin Exp Pathol 2018 1;11(12):5923-5937. Epub 2018 Dec 1.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University Nanning, Guangxi, People's Republic of China.

Little is known about the association of monoacylglycerol acyltransferase 1 gene () rs634501 single nucleotide polymorphism (SNP) and serum lipid profiles in the Chinese populations. The aim of this study was to detect the association of the rs634501 SNP and several environmental factors with serum lipid levels in the Chinese Maonan and Han populations. Genotypes of the SNP in 2014 unrelated participants (Han, 986; Maonan, 1028) were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and confirmed by direct sequencing. The genotypic and allelic frequencies of the rs634501 SNP were significantly different between the Han and Maonan populations as well as between males and females in the Maonan population. The A allele carriers had lower serum apolipoprotein (Apo) A1 levels, the ApoA1/ApoB ratio and higher ApoB levels in Maonans; and lower high-density lipoprotein cholesterol, ApoA1 levels, ApoA1/ApoB ratio, and higher triglyceride levels in Han than the A allele non-carriers. There were also different associations of the rs634501 SNP and serum lipid profiles between males and females in the both ethnic groups. Serum lipid parameters in the two ethnic groups were also associated with several environmental factors. These results suggest that the association of the rs634501 SNP and serum lipid parameters might have ethnic- and/or sex-specificity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963053PMC
December 2018

The CXCL12 SNPs and their haplotypes are associated with serum lipid traits.

Sci Rep 2019 12 20;9(1):19524. Epub 2019 Dec 20.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China.

The relationship among the single nucleotide polymorphisms (SNPs) of the C-X-C motif chemokine ligand 12 gene (CXCL12) and the serum lipid profiles in the Chinese population has rarely been described, especially in somewhat old-fashioned and isolated Maonan minority. The goal of the current study was to elucidate the connection among the CXCL12 rs501120 and rs1746048 SNPs, haplotypes, several environmental factors and serum lipid traits in the Maonan as well as Han populations. Genotyping of the two SNPs, gel electrophoresis and direct sequencing were accomplished in 1,494 distinct subjects (Maonan, 750 and Han, 744) using polymerase chain reaction and restriction fragment length polymorphism. The frequencies of genotypes as well as alleles of the two SNPs were not similar between the two ethnic groups. The rs501120 SNP was related with serum total cholesterol levels, while the rs1746048 SNP was related with serum apolipoprotein (Apo) B levels. Four haplotypes were identified, of which the rs501120A-rs1746048C haplotype was the most common. The haplotypes of rs501120A-rs1746048T increased and rs501120G-rs1746048C decreased the risk of hyperlipidemia (P < 0.001 for each), showing consistent association with the levels of serum triglyceride, ApoA1 and ApoB. These outcomes specify that the CXCL12 SNPs as well as their haplotypes are related to serum lipid levels. Different serum lipid levels between both populations may partially be related to the CXCL12 SNPs, their haplotypes along with several environmental factors.
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http://dx.doi.org/10.1038/s41598-019-55725-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925251PMC
December 2019

Correlation Between the rs1042034 SNP and Blood Lipid Characteristics of 2 Ethnic Groups in China.

Clin Appl Thromb Hemost 2019 Jan-Dec;25:1076029619892088

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.

The apolipoprotein (Apo) B gene () is a susceptible gene for dyslipidemia. The purpose of this investigation was to explore the relationship between the rs1042034 single-nucleotide polymorphism (SNP) and serum lipid levels in the Maonan and Han populations. A total of 598 Maonan participants and 609 Han participants were genotyped by polymerase chain reaction and restriction fragment length polymorphism, and the genotypes were also verified by sequencing. There were no differences in genotype and allele frequencies between the 2 ethnic groups or between males and females. The levels of triglyceride (TG) in Maonans were higher and high-density lipoprotein cholesterol was lower in the A allele carriers than the A allele noncarriers; the A allele carriers in Hans had higher TG levels and lower ApoA1/ApoB ratio than the A allele noncarriers ( < .05 for all). Subgroup analysis showed that the A allele carriers in Maonan females had higher TG levels and the A allele carriers in Han females had higher TG levels and lower ApoA1/ApoB ratio than the A allele noncarriers ( < .05 for all). In our study populations, there may be ethnicity- and/or sex-specific associations between the rs1042034 SNP and serum lipid levels.
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http://dx.doi.org/10.1177/1076029619892088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019501PMC
May 2020

A novel circRNA-miRNA-mRNA network identifies circ-YOD1 as a biomarker for coronary artery disease.

Sci Rep 2019 12 4;9(1):18314. Epub 2019 Dec 4.

Clinical Laboratory of the Affiliated Cancer Hospital, Guangxi Medical University, 71 Hedi Road, Nanning, 530021, Guangxi, China.

Circular RNAs (circRNAs) are involved in many physiological functions. Whether circulating circRNAs serve as markers for coronary artery disease (CAD) is unknown. Seven CAD-related microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and were analyzed using clustering and functional enrichment to identify hub mRNAs and miRNAs. StarBase V3.0 and circinteractome databases were used to predict interactions between circRNAs and miRNAs whereas miRwalk and DIANA TOOLS were used to predict interactions between miRNAs and mRNAs. Altogether, this helped establish a circRNA-miRNA-mRNA triple network for diagnosis of CAD. Five non-coding RNAs (ncRNAs) were identified in our study population with the use of quantitative real-time PCR (RT-PCR). The prognostic values of circYOD1, hsa-miR-21-3p and hsa-miR-296-3p were evaluated using a receiver operating characteristic (ROC) curve. A CAD circRNA-miRNA-mRNA network was established from our analyses containing one circRNA, four miRNAs and thirteen mRNAs. After performing RT-PCR validation between CAD and non-CAD samples, only three ncRNAs of five ncRNAs showed significance for further analysis. The area under ROC curve (AUC) of circ-YOD1 was 0.824, the AUC of hsa-miR-21-3p was 0.731 and hsa-miR-296-3p was 0.776. The pairwise comparison results showed that circ-YOD1 had statistical significance (P < 0.01 and P < 0.05). The results of functional enrichment analysis of interacting genes and microRNAs showed that the shared circ-YOD1 may act as a new biomarker for CAD. Our investigation of the triple regulatory networks of circRNA-miRNA-mRNA in CAD revealed circ-YOD1 as a potential biomarker for CAD.
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http://dx.doi.org/10.1038/s41598-019-54603-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892882PMC
December 2019

Potential molecular mechanism of ACE gene at different time points in STEMI patients based on genome-wide microarray dataset.

Lipids Health Dis 2019 Oct 23;18(1):184. Epub 2019 Oct 23.

Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.

Background: This study aimed to investigate the angiotensin converting enzyme (ACE) co-expression genes and their pathways involved in ST-segment elevation myocardial infarction (STEMI) at different time points.

Methods: The array data set of GSE59867 was examined for the ACE co-expression genes in peripheral blood samples from 111 patients with STEMI at four time points (admission, discharge, and 1 and 6 months after MI). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Gene Ontology (GO) annotation and protein-protein interaction (PPI) of the co-expression genes were determined using online analytical tools. The Cytoscape software was used to create modules and hub genes.

Results: The number of biological processes (BP), cellular components (CC) and molecular functions (MF) was 43, 22 and 24 at admission; 18, 19 and 11 at discharge; 30, 37 and 21 at 1 month after MI; and 12, 19 and 14 at 6 months after MI; respectively. There were 6 BP, 8 CC and 4 MF enriched at every time point. The co-expression genes were substantially enriched in 12, 5, 6 and 14 KEGG pathways at the four time points, respectively, but no KEGG pathway was found to be common in all time points. We identified 132 intersectional co-expression genes (90 positive and 42 negative) from the four time points and 17 BP, 13 CC, 11 MF and 7 KEGG pathways were enriched. In addition, the PPI network contained 129 nodes and 570 edges, and only 1 module was identified to be significantly enriched in just 1 BP (chromatin-mediated maintenance of transcription).

Conclusions: The results of the present study showed that the ACE co-expression genes and their pathways involved in STEMI were significantly different at four different time points. These findings may be helpful for further understanding the functions and roles of ACE in different stages of STEMI, and providing reference for the treatment of STEMI.
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http://dx.doi.org/10.1186/s12944-019-1131-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813054PMC
October 2019

Association between the XKR6 rs7819412 SNP and serum lipid levels and the risk of coronary artery disease and ischemic stroke.

BMC Cardiovasc Disord 2019 08 20;19(1):202. Epub 2019 Aug 20.

Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China.

Background: The present study aimed to expound the association between the XK related 6 gene (XKR6) rs7819412 single nucleotide polymorphism (SNP) and serum lipid profiles and the risk of coronary artery disease (CAD) and ischemic stroke.

Methods: The genetic makeup of the XKR6 rs7819412 SNP in 1783 unrelated participants (controls, 643; CAD, 588 and ischemic stroke, 552) of Han Chinese was obtained by the Snapshot technology.

Results: The genotypic frequencies of the SNP were disparate between CAD (GG, 81.0%; GA/AA, 19.0%) or ischemic stroke (GG, 81.2%; GA/AA, 18.8%) patients and healthy controls (GG, 85.7%, GA/AA, 14.3%; P < 0.05 vs. CAD or ischemic stroke; respectively). The A allele frequency was also diverse between CAD (10.1%) or ischemic stroke (10.0%) and control groups (7.5%; P < 0.05 vs. CAD or ischemic stroke; respectively). The GA/AA genotypes and A allele were associated with high risk of CAD and ischemic stroke (CAD: P = 0.026 for GA/AA vs. GG, P = 0.024 for A vs. G; Ischemic stroke: P = 0.029 for GA/AA vs. GG, P = 0.036 for A vs. G). The GA/AA genotypes were also associated with increased serum triglyceride (TG) concentration in CAD and total cholesterol (TC) concentration in ischemic stroke patients.

Conclusions: These data revealed that the XKR6 rs7819412 A allele was related to increased serum TG levels in CAD, TC levels in ischemic stroke patients and high risk of CAD and ischemic stroke.
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http://dx.doi.org/10.1186/s12872-019-1179-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700994PMC
August 2019

rs6882076 SNP Is Associated with Decreased Levels of Triglycerides and the Risk of Coronary Heart Disease and Ischemic Stroke.

Int J Med Sci 2019 2;16(6):864-871. Epub 2019 Jun 2.

Clinical Laboratory of the Affiliated Cancer Hospital, Guangxi Medical University, 71 Hedi Road, Nanning 530021, Guangxi, China.

: The T-cell immunoglobulin and mucin domain 4 gene () rs6882076 single nucleotide polymorphism (SNP) has been associated with serum total cholesterol, low-density lipoprotein cholesterol and triglycerides (TG) levels, but the results are inconsistent. Moreover, little is known about such association in Chinese populations. The aim of this study was to detect the association of the rs6882076 SNP and serum lipid levels and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Southern Chinese Han population. : Genotypes of the rs6882076 SNP in 1765 unrelated subjects (CHD, 581; IS, 559 and healthy controls, 625) were determined by the Snapshot Technology. : The genotypic and allelic frequencies of the rs6882076 SNP were different between the CHD/IS patients and controls ( < 0.05 for all). The subjects with CT/TT genotypes were associated with decreased risk of CHD ( = 0.014 for CT/TT . CC genotypes, = 0.010 for T . C alleles) and IS ( = 0.003 for CT/TT . CC genotypes; = 0.016 for T . C alleles). The T allele carriers in healthy controls were also associated with decreased levels of serum TG. : The results of the present study suggest that the rs6882076 SNP is associated with decreased risk of CHD and IS in our study population. It is likely to decrease the CHD and IS risk by reducing serum TG levels.
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http://dx.doi.org/10.7150/ijms.31729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643107PMC
February 2020

A novel lncRNA-miRNA-mRNA triple network identifies lncRNA as an important regulator of miRNA and gene expression in coronary artery disease.

Nutr Metab (Lond) 2019 6;16:39. Epub 2019 Jun 6.

1Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021 Guangxi People's Republic of China.

Background: Long non-coding RNAs (lncRNAs) are involved in numerous physiological functions. Yet, their mechanisms in coronary artery disease (CAD) are not well understood.

Methods: The expression profile of genes associated to CAD was reannotated into the lncRNA-mRNA biphasic profile. The target microRNA data were used to design a global CAD triple network. Thereafter, we conducted a functional enrichment analysis and clustering using the triple network from the level of topology analyses. The expression of four non-coding RNAs (ncRNAs) was measured by qRT-PCR and the risk of CAD was calculated by nomogram. The prognostic value of three ncRNAs was evaluated using receiver operating characteristic (ROC) curve.

Results: A CAD lncRNA-miRNA-mRNA network was constructed which included 15 mRNAs, 3 miRNAs, 19 edges and one lncRNA. Nomogram showed that four ncRNAs were the risk of CAD. After RT-PCR validation in four ncRNAs between CAD and non-CAD samples, only three ncRNAs had significant meaning for further analysis. ROC curve showed that presented an area under curve (AUC) of 0.862, the AUC of hsa -miR-142-3p was 0.856 and hsa -miR126-5p was 0.822. After the pairwise comparison, we found that had significant statistical significance ( < 0.05 and  < 0.01. The results of functional enrichment analysis of interacting gene and microRNA showed that the shared lncRNA may be a new factor for CAD.

Conclusions: This investigation on the regulatory networks of lncRNA-miRNA-mRNA in CAD suggests that a novel lncRNA, lncRNA is a risk factor for CAD, and expands our understanding into the mechanisms involved in the pathogenesis of CAD.
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http://dx.doi.org/10.1186/s12986-019-0366-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555741PMC
June 2019

Integrated analysis of gene expression changes associated with coronary artery disease.

Lipids Health Dis 2019 Apr 9;18(1):92. Epub 2019 Apr 9.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China.

Background: This study investigated the pathways and genes involved in coronary artery disease (CAD) and the associated mechanisms.

Methods: Two array data sets of GSE19339 and GSE56885 were downloaded. The limma package was used to analyze the differentially expressed genes (DEGs) in normal and CAD specimens. Examination of DEGs through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology annotation was achieved by Database for Annotation, Visualization and Integrated Discovery (DAVID). The Cytoscape software facilitated the establishment of the protein-protein interaction (PPI) network and Molecular Complex Detection (MCODE) was performed for the significant modules.

Results: We identified 413 DEGs (291 up-regulated and 122 down-regulated). Approximately 256 biological processes, only 1 cellular component, and 21 molecular functions were identified by GO analysis and 10 pathways were enriched by KEGG. Moreover, 264 protein pairs and 64 nodes were visualized by the PPI network. After the MCODE analysis, the top 4 high degree genes, including interleukin 1 beta (IL1B, degree = 29), intercellular adhesion molecule 1 (ICAM1, degree = 25), Jun proto-oncogene (JUN, degree = 23) and C-C motif chemokine ligand 2 (CCL2, degree = 20) had been identified to validate in RT-PCR and Cox proportional hazards regression between CAD and normals.

Conclusions: The relative expression of IL1B, ICAM1 and CCL2 was higher in CAD than in normal controls (P < 0.05-0.001), but only IL1B and CCL2 genes were confirmed after testing the gene expression in blood and/or analyzing in Cox proportional hazards regression (P < 0.05-0.001), and the proper mechanism may involve in the AGE-RAGE signaling pathway, fluid shear stress, the tumor necrosis factor (TNF) and cytokine-cytokine receptor interaction.
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http://dx.doi.org/10.1186/s12944-019-1032-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454774PMC
April 2019

Integrated DNA methylation and gene expression analysis in the pathogenesis of coronary artery disease.

Aging (Albany NY) 2019 03;11(5):1486-1500

Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, China.

To evaluate DNA methylation sites and gene expression associated with coronary artery disease (CAD) and the possible pathological mechanism involved, we performed (1) genome-wide DNA methylation and mRNA expression profiling in peripheral blood datasets from the Gene Expression Omnibus repository of CAD samples and controls; (2) functional enrichment analysis and differential methylation gene regulatory network construction; (3) validation tests of 11 differential methylation positions of interest and the corresponding gene expression; and (4) correlation analysis for DNA methylation and mRNA expression data. A total of 669 differentially expressed mRNAs were matched to differentially methylated genes. After disease ontology, Kyoto Encyclopedia of Genes and Genomes pathway, gene ontology, protein-protein interaction and network construction and module analyses, 11 differentially methylated positions (DMPs) corresponding to 11 unique genes were observed: - cg26949694, - cg24381155, - cg02223351, - cg11267527, - cg27637738, - cg13104385, - cg20545410, - cg25613180, - cg00559992, - cg27178677 and - cg09247619. After validation tests of 11 DMPs of interest and the corresponding gene expression, we found that was less hypomethylated in the CAD group, whereas the relative expression of , and was lower in CAD samples, and and methylation was negatively correlated with their expression. This study identified the correlation between DNA methylation and gene expression and highlighted the importance of in CAD pathogenesis.
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http://dx.doi.org/10.18632/aging.101847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428103PMC
March 2019

TRIB1 and TRPS1 variants, G × G and G × E interactions on serum lipid levels, the risk of coronary heart disease and ischemic stroke.

Sci Rep 2019 02 20;9(1):2376. Epub 2019 Feb 20.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China.

This study aimed to assess the association of the tribbles pseudokinase 1 (TRIB1) and transcriptional repressor GATA binding 1 (TRPS1) single nucleotide polymorphisms (SNPs) and the gene-gene (G × G) and gene-environment (G × E) interactions with serum lipid levels, the risk of coronary heart disease (CHD) and ischemic stroke (IS) in the Guangxi Han population. Genotyping of the rs2954029, rs2980880, rs10808546, rs231150, rs2737229 and rs10505248 SNPs was performed in 625 controls and 1146 unrelated patients (CHD, 593 and IS, 553). The genotypic and allelic frequencies of some SNPs were different between controls and patients (CHD, rs2954029 and rs231150; IS, rs2954029 and rs2980880; P < 0.05-0.01). Two SNPs were associated with increased risk of CHD (rs2954029 and rs231150) and IS (rs2954029) in different genetic models. Several SNPs in controls were associated with total cholesterol (rs2954029, rs2980880 and rs2737229), triglyceride (rs2954029 and rs10808546), low-density lipoprotein cholesterol (rs2954029), high-density lipoprotein cholesterol (rs2980880 and rs231150) and apolipoprotein A1 (rs2737229) levels. The rs2954029TA/AA-age (>60 year) interaction increased the risk of CHD, whereas the rs10808546CT/TT-drinking interaction decreased the risk of IS. The rs2954029A-rs2980880C-rs10808546C haplotype was associated with increased risk of CHD and IS. The rs2954029A-rs2980880T-rs10808546C haplotype was associated with increased risk of CHD. The rs2954029-rs231150 interactions had an increased risk of both CHD and IS. These results suggest that several TRIB1 and TRPS1 SNPs were associated with dyslipidemia and increased risk of CHD and IS in our study population. The G × G and G × E interactions on serum lipid levels, and the risk of CHD and IS were also observed.
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http://dx.doi.org/10.1038/s41598-019-38765-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382757PMC
February 2019

Association between the LIPG polymorphisms and serum lipid levels in the Maonan and Han populations.

J Gene Med 2019 02 4;21(2-3):e3071. Epub 2019 Feb 4.

Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China.

Introduction: The Maonan population is a relatively isolated minority in China. Little is known about endothelial lipase gene (LIPG) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. The present study aimed to detect the association of several LIPG SNPs and environmental factors with serum lipid levels in the Chinese Maonan and Han populations.

Methods: In total, 773 subjects of Maonan ethnicity and 710 participants of Han ethnicity were randomly selected from our previous stratified randomized samples. Genotypes of the LIPG rs2156552, rs4939883 and rs7241918 SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism, and then confirmed by direct sequencing.

Results: The allelic (rs2156552, rs4939883 and rs7241918) and genotypic (rs2156552 and rs4939883) frequencies were different between the two ethnic groups (p < 0.05-0.01). The minor allele carriers had lower apolipoprotein (Apo)A1/ApoB ratio (rs2156552 and rs7241918), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo)A1 (rs2156552) levels and higher ApoB levels (rs4939883) in the Han population, and lower HDL-C (rs2156552, rs4939883 and rs7241918) levels in the Maonan minority than the minor allele non-carriers (p < 0.0167 after Bonferroni correction). Subgroup analyses according to sex showed that the minor allele carriers had a lower ApoA1/ApoB ratio (rs2156552 and rs7241918) and higher ApoB levels (rs7241918) in Han males, and lower ApoA1 and HDL-C levels in Maonan females than the minor allele non-carriers (p < 0.0167-0.001).

Conclusions: The present study demonstrates the association between the LIPG polymorphsims and serum lipid levels in the two ethnic groups. These associations might have an ethnic- and or/sex-specificity.
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http://dx.doi.org/10.1002/jgm.3071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590183PMC
February 2019

Circulating miR-3659 may be a potential biomarker of dyslipidemia in patients with obesity.

J Transl Med 2019 01 14;17(1):25. Epub 2019 Jan 14.

Department of Molecular Genetics, Medical Scientific Research Center, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China.

Background: The present study attempted to identify potential key genes and miRNAs of dyslipidemia in obese, and to investigate the possible mechanisms associated with them.

Methods: The microarray data of GSE66676 were downloaded, including 67 obese samples from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network (WGCNA) analysis was performed using WGCNA package and grey60 module was considered as the highest correlation. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for this module were performed by clusterProfiler and DOSE package. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using molecular complex detection.

Results: Collagen type I alpha 1 chain gene (COL1A1) had the best significant meaning. After bioinformatic analysis, we identified four miRNAs (hsa-miR-3659, hsa-miR-4658, hsa-miR151a-5p and hsa-miR-151b) which can bind SNPs in 3'UTR in COL1A1. After validation with RT-qPCR, only two miRNAs (hsa-miR-3659 and hsa-miR151a-5p) had statistical significance.

Conclusions: The area of 0.806 for miR-3659 and 0.769 for miR-151a-5p under the ROC curve (AUC) may have good diagnostic value for dyslipidemia. Circulating miR-3659 may be a potential biomarker of dyslipidemia in patients with obesity.
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http://dx.doi.org/10.1186/s12967-019-1776-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332685PMC
January 2019

LIPG SNPs, their haplotypes and gene-environment interactions on serum lipid levels.

Lipids Health Dis 2019 Jan 8;18(1):10. Epub 2019 Jan 8.

Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.

Background: Maonan nationality is a relatively conservative and isolated minority in the Southwest of China. Little is known about the association of endothelial lipase gene (LIPG) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations.

Methods: A total of 1280 subjects of Maonan nationality and 1218 participants of Han nationality were randomly selected from our previous stratified randomized samples. Genotypes of the four LIPG SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism, and then confirmed by direct sequencing.

Results: Several SNPs were associated with high-density lipoprotein cholesterol (rs3813082, rs2000813 and rs2097055) in the both ethnic groups; total cholesterol and apolipoprotein (Apo) A1 (rs2000813) in Han nationality; and low-density lipoprotein cholesterol, ApoB, triglyceride (rs2097055) and ApoA1 (rs3819166) in Maonan minority (P < 0.0125 for all after Bonferroni correction). The commonest haplotype was rs3813082T-rs2000813C-rs2097055T-rs3819166A (Han, 44.2% and Maonan, 48.7%). The frequencies of the T-C-T-A, T-C-T-G, T-T-C-G and G-T-C-G haplotypes were different between the Maonan and Han populations (P < 0.05-0.001). The associations between haplotypes and dyslipidemia were also different in the Han and/or Maonan populations (P < 0.05-0.001).

Conclusions: The differences in serum lipid profiles between the two ethnic groups might partly be attributed to these LIPG SNPs, their haplotypes and gene-environmental interactions.

Trial Registration: Retrospectively registered.
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http://dx.doi.org/10.1186/s12944-018-0942-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325827PMC
January 2019

Erratum: The association between the rs10248618 SNP and serum lipid traits, the risk of coronary artery disease, and ischemic stroke.

Int J Clin Exp Pathol 2018 1;11(12):6049. Epub 2018 Dec 1.

Department of Neurology, The First Affiliated Hospital, Guangxi Medical University Nanning, Guangxi, China.

[This corrects the article on p. 4585 in vol. 11, PMID: 31949857.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090253PMC
December 2018

variants and their haplotypes are associated with serum lipid levels, the risk of coronary artery disease and ischemic stroke and atorvastatin cholesterol-lowering responses.

Nutr Metab (Lond) 2018 5;15:70. Epub 2018 Oct 5.

1Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021 Guangxi People's Republic of China.

Background: This study aimed to assess the association between the angiopoietin-like protein 4 gene () single nucleotide polymorphisms (SNPs) and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS), and response to atorvastatin therapy in a Southern Chinese Han population.

Methods: Genotypes of the rs4076317, rs7255436, rs1044250 and rs2967605 SNPs in 1,654 unrelated subjects (CAD, 568; IS, 537; and controls, 549) were determined by the Snapshot technology. Another group of 724 hyperlipidemic patients was selected and treated with atorvastatin calcium tablet 20 mg/day for 8 weeks.

Results: The rs2967605 CT/TT genotypes were associated with a decreased risk of CAD (adjusted OR = 0.68, 95% CI = 0.47-0.99, = 0.043 for CT/TT . CC) and IS (adjusted OR = 0.55, 95% CI = 0.38-0.80, = 0.020 for CT/TT . CC). There was no significant association between the four SNPs and angiographic severity of CAD. The subjects with the rs4076317 CG/CC genotypes in controls had higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than the subjects with the GG genotype ( < 0.001; a < 0.0018 was regarded statistically significant by the Bonferroni correction). The subjects with rs4076317CG/GG genotypes had lower TC and LDL-C levels than the subjects with CC genotype after atorvastatin treatment ( < 0.001).

Conclusions: The observed associations suggest that the variants have a potential role on serum lipid levels and atherosclerosis-related diseases in the Chinese Han population, especially the rs4076317 and rs2967605 SNPs.
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http://dx.doi.org/10.1186/s12986-018-0308-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173870PMC
October 2018

rs1407977 SNP is associated with the risk of coronary heart disease and ischemic stroke.

Int J Clin Exp Pathol 2018 1;11(10):5044-5053. Epub 2018 Oct 1.

Department of Neurology, The First Affiliated Hospital, Guangxi Medical University Nanning, Guangxi, People's Republic of China.

Previous genome-wide association studies have showed that several tetratricopeptide repeat domain protein 39B gene () single nucleotide polymorphisms (rs581080 and rs471364) were associated with serum high-density lipoprotein cholesterol levels among populations of European ancestry, but the results are inconsistent. Furthermore, little is known about the association between SNPs and the susceptibility to coronary heart disease (CHD) and ischemic stroke (IS). Therefore, this study was undertaken to detect the association between the rs1407977 SNP and serum lipid levels and the risk of CHD and IS in a Southern Chinese Han population. Genotyping of the SNP in 1741 unrelated subjects (healthy controls, 624; CHD patients, 578 and IS patients, 539) was performed by the Snapshot Technology. The genotypic and allelic frequencies of the SNP were different between the control subjects and CHD patients, or between the control subjects and IS patients ( ≤ 0.001). The T allele frequency was higher in CHD (16.2%) and IS (15.0%) patients than in controls (9.8%). The T allele carriers had higher risk of CHD (OR = 1.728, 95% CI = 1.290-2.316, < 0.001) and IS (OR = 1.518, 95% CI = 1.182-2.116, = 0.002) than the T allele non-carriers after controlling for potential confounders. No significant association was observed between the rs1407977 SNP and all seven serum lipid traits. These results suggest that the rs1407977 SNP is associated with the risk of CHD and IS in our study population and does not depend on serum lipid levels.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962934PMC
October 2018

The association between the rs10248618 SNP and serum lipid traits, the risk of coronary artery disease, and ischemic stroke.

Int J Clin Exp Pathol 2018 1;11(9):4585-4594. Epub 2018 Sep 1.

Department of Neurology, The First Affiliated Hospital, Guangxi Medical University Nanning, Guangxi, China.

Previous genome-wide association studies have shown that the rs10248618 single nucleotide polymorphism (SNP) in the dynein axonemal heavy chain 11 gene () has been associated with serum high-density lipoprotein cholesterol (HDL-C) levels. However, little is known about such association in the Chinese population. The present study was performed to clarify the association between the rs10248618 SNP and serum lipid traits and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Genotypes of the rs10248618 SNP in 1,213 unrelated patients (CAD, 600 and IS, 613) and 631 healthy controls were determined by snapshot technology. The genotypic and allelic frequencies of the SNP were significantly different between the CAD/IS patients and the controls ( < 0.01 for all). The CT/TT genotypes and the T allele were associated with an increased risk of CAD and IS (CAD: < 0.01 for CT/TT CC and T C; IS: < 0.01 for CT/TT CC and T C). The CT/TT genotypes in the healthy controls, but not in CAD or IS patients, were associated with a decreased serum HDL-C and apolipoprotein (Apo) A1 concentration. These results suggest that the rs10248618 SNP is associated with the risk of CAD and IS in our study population. It is likely to increase the risk of CAD and IS by reducing serum HDL-C and ApoA1 levels.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962952PMC
September 2018