Publications by authors named "Tianbo Jin"

255 Publications

CYP2S1 gene methylation among High-altitude pulmonary edema.

Gene 2022 Aug 25;834:146590. Epub 2022 May 25.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China; School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi 712082, China; Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, China. Electronic address:

Background: High altitude pulmonary edema (HAPE) is a fatal disease of fluid accumulation in the lungs resulting from acute exposure to high altitude and hypoxia. Now research has found that changes in DNA methylation are genetically related. We investigated the effects of hypermethylation and hypomethylation on HAPE.

Methods: We conducted an analysis of methylation in Chinese HAPE patients (53 patients and 53 controls). EpiTYPER of the Sequenom MassARRAY platform was used to detect DNA methylation at 43 CpG sites in CYP2S1.

Results: We used probability analysis to find that only five CPG sites were not methylated. CYP2S1_1_CpG_11, CYP2S1_2_CpG_11, CYP2S1_2_CpG_12, CYP2S1_2_CpG_13, and CYP2S1_3_CPG_11.12 in the case group were lower than those in the control group. Our results showed that, 12 CpG sites had different methylation levels in HAPE patients compared with healthy controls, and only CYP2S1_1_CPG_1.2.3 (OR = 2.920, 95 %Cl = 1.228-6.946, p = 0.015) had a higher risk of hypermethylation than hypomethylation. ROC curve analysis showed that the methylation level of CYP2S1 could effectively predict the risk of HAPE patients.

Conclusion: Our results showed that several CpG sites in the promoter regions of CYP2S1 gene were abnormally methylated in HAPE patients.
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http://dx.doi.org/10.1016/j.gene.2022.146590DOI Listing
August 2022

Missense Variant rs28362680 in Reduces Risk of Coronary Heart Disease.

Pharmgenomics Pers Med 2022 6;15:449-464. Epub 2022 May 6.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an, Shaanxi, 710069, People's Republic of China.

Background: The pathological basis of coronary heart disease (CHD) is atherosclerosis. can inhibit the activation of T cells. We aimed to explore the association between genetic variants and CHD risk in the southern Chinese Han population.

Methods: We recruited 1419 participants to perform an association analysis between missense variants in and CHD risk through SNPStats online software. Genotyping of all candidate SNPs were completed by the Agena MassARRAY. In addition, we used false-positive report probability analysis to detect whether the positive findings were noteworthy observations. We also used Haploview 4.2 software and SNPStats online software to conduct the haplotype analysis and analysis of linkage disequilibrium (LD). Finally, the interaction of SNP-SNP in CHD risk was evaluated by multi-factor dimensionality reduction (MDR).

Results: The results showed that -rs35624343, -rs117896888, -rs41441651, -rs41417449, -rs28362680 and -rs2076523 were significantly associated with the CHD susceptibility. Especially for -rs28362680, the allele A (OR = 0.68, < 0.0001), genotype AA (OR = 0.40, = 0.001) or GA (OR = 0.68, < 0.0001) were associated with the reducing CHD risk. And -rs28362680 significantly reduced the CHD risk under all genetic models (dominant: OR = 0.64, < 0.0001; recessive: OR = 0.47, = 0.003; overdominant: OR = 0.73, = 0.004; log-additive: OR = 0.66, < 0.0001). And -rs28362680 was also closely associated with CHD risk reduction in all stratified analyses (age, gender, smoking, drinking, hypertension and diabetes). In addition, haplotype analysis showed that the "CCTA" (OR = 0.65, < 0.0001) and "GTCA" (OR = 0.68, = 0.013) may reduce CHD risk.

Conclusion: Missense variants (rs35624343, rs117896888, rs41441651, rs41417449, rs28362680, rs2076523) may be protective factors for the CHD risk. In particular, there were sufficient evidences that BTNL2-rs28362680 can protective CHD risk.
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http://dx.doi.org/10.2147/PGPM.S353085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091699PMC
May 2022

Relationship between rs7586085, GALNT3 and CCDC170 gene polymorphisms and the risk of osteoporosis among the Chinese Han population.

Sci Rep 2022 04 12;12(1):6089. Epub 2022 Apr 12.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an, Shaanxi, 710069, China.

Osteoporosis (OP) has plagued many women for years, and bone density loss is an indicator of OP. The purpose of this study was to evaluate the relationship between the polymorphism of the rs7586085, CCDC170 and GALNT3 gene polymorphisms and the risk of OP in the Chinese Han population. Using the Agena MassArray method, we identified six candidate SNPs on chromosomes 2 and 6 in 515 patients with OP and 511 healthy controls. Genetic model analysis was performed to evaluate the significant association between variation and OP risk, and meanwhile, the multiple tests were corrected by false discovery rate (FDR). Haploview 4.2 was used for haplotype analysis. In stratified analysis of BMI ˃ 24, rs7586085, rs6726821, rs6710518, rs1346004, and rs1038304 were associated with the risk of OP based on the results of genetic models among females even after the correction of FDR (q < 0.05). In people at age ≤ 60 years, rs1038304 was associated with an increased risk of OP under genetic models after the correction of FDR (q < 0.05). Our study reported that GALNT3 and CCDC170 gene polymorphisms and rs7586085 are the effective risk factors for OP in the Chinese Han population.
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http://dx.doi.org/10.1038/s41598-022-09755-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005502PMC
April 2022

Genetic variation of pharmacogenomic VIP variants in the Chinese Li population: an updated research.

Mol Genet Genomics 2022 Mar 11;297(2):407-417. Epub 2022 Feb 11.

Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University, Xi'an, 710069, Shaanxi, China.

Previous studies have shown that the frequency of very important pharmacogenomic (VIP) genes varies in different populations which leads to the diversities in drug efficacy, safety, and the risk associated with adverse drug reactions (ADRs). The purpose of this study was to identify the distribution differences of VIP variants between the Li population and the other 13 populations. Based on the Pharmacogenomics Knowledgebase database (PhamGKB), we successfully genotyped 52 VIP variants within 27 genes in 200 unrelated Li population. χ test was used to evaluate the significant differences of genotype and allele frequencies between the Li and the other 13 populations from 1000 Genomes Project. Our study showed that the genotype frequencies of single nucleotide polymorphisms (SNPs) on KCNH2, ACE, CYP4F2, and CYP2E1 were considerably different between Li and the other 13 populations, especially in rs1805123 (KCNH2), rs4291 (ACE), rs3093105 (CYP4F2), and rs6413432 (CYP2E1) loci. Meanwhile, we found several VIP variants that might alter the drug metabolism of cisplatin-cyclophosphamide (CYP2E1), vitamin E (CYP4F2), asthma amlodipine, chlorthalidone, and lisinopril (ACE) through PharmGKB. We also identified other variants which were associated with adverse effects in isoniazid and rifampicin (CYP2E1; hepatotoxicity). The four loci rs1805123 (KCNH2), rs4291 (ACE), rs3093105 (CYP4F2), and rs6413432 (CYP2E1) provided a reliable basis for the prediction of the efficacy of certain drugs. The study complemented the existed pharmacogenomics information, which could provide theoretical basis for predicting the efficacy of certain drugs in the Li population.
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http://dx.doi.org/10.1007/s00438-022-01855-9DOI Listing
March 2022

Genome-wide association study of serum tumor markers in Southern Chinese Han population.

BMC Cancer 2022 Feb 10;22(1):160. Epub 2022 Feb 10.

Department of General Practice, Hainan General Hospital, #19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, P.R. China.

Background: Serum indicators AFP, CA50, CA125, CA153, CA19-9, CEA, f-PSA, SCC-Ag have been confirmed as tumor markers (TMs). We conducted a genome-wide association study on 8 tumor markers of our 427 Han population in southern China, in order to identify genetic loci that are significantly associated with the level of 8 tumor markers.

Methods: We use Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. We used IMPUTE2 software for imputation, and 1000 Genomes Project (Phase 3) was used as haplotype reference. After necessary quality control and statistical analysis, genetic loci genome-wide associated with TMs (p < 5E-8) will be identified. Finally, we selected Top SNPs (p < 5E-7) from the GWAS results for replication test. We used SPSS software to draw the distribution box plots of serum TMs under different genotypes of significant loci.

Results: The results showed that there were only MUC1 (mucin 1)-rs4072037 significantly genome-wide associated with CA153 (p = 1.28E-18). However, we found that a total of 30 genetic loci have a suggestively significant genome-wide association with the level of 8 serum tumor markers (p < 5E-6). Then 3 Top SNPs (p < 5E-7) were selected for replication verification. The results showed that MUC1-rs4072037 was still significantly associated with CA153 in another population (p = 3.73E-08). Comparing with the TT genotype of rs4072037, the CA153 level was higher under CC or CT genotype of rs4072037.

Conclusion: MUC1-rs4072037 is significantly genome-wide associated with CA153 level. There are 30 genetic loci suggestively genome-wide associated with level of tumor markers among the Han population from Southern China.
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http://dx.doi.org/10.1186/s12885-022-09236-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832811PMC
February 2022

Effect of PITX2 genetic variants on the susceptibility to stroke in the Chinese Han population.

Infect Genet Evol 2022 03 4;98:105201. Epub 2022 Jan 4.

College of Life Sciences, Northwest University, Xi'an, Shaanxi province 710069, China; Quality Control Department, Internal Medicine-Neurology, Xi'an First Hospital, First Affiliated Hospital of Northwestern University, Xi'an, Shaanxi province 710002, China. Electronic address:

Purpose: Stroke is a multifactorial and complex disease caused by the obstruction or rupture of cerebrovascular. To explore the influence of genetic factors on stroke susceptibility, we investigated the association between four single nucleotide polymorphisms (SNPs) in the paired-like homeodomain transcription factor 2 (PITX2) gene and stroke risk.

Methods: A total of 977 volunteers including 476 stroke patients and 501 control individuals were recruited. The association between PITX2 polymorphisms and stroke risk was evaluated using genetic models and haplotype analyses. The strength of the association between each studied polymorphisms and stroke risk was evaluated by calculating odds ratios (ORs) and 95% confidence intervals (CIs). What's more, multifactor dimensionality reduction (MDR) was used to predict the interaction between SNPs.

Results: Our study showed that rs6817105 in PITX2 was related to a significant increase in stroke susceptibility (OR = 1.42, 95% CI = 1.04-1.94, p = 0.028). Stratified analyses based on gender indicated that rs6817105, rs13143308, and rs6843082 polymorphisms were significantly associated with an increased risk of stroke in male (OR = 0.68, 95% CI = 0.47-0.99, p = 0.042; OR = 0.53, 95% CI = 0.30-0.96, p = 0.035; and OR = 0.55, 95% CI = 0.30-0.99, p = 0.047). Besides, SNP rs6817105 was significantly increased the risk of stroke in people at age over 65 years (OR = 1.87, 95% CI =1.12-3.11, p = 0.016). MDR showed that the interaction model of rs6817105 and rs3853445 emerged as the best predictor between the PITX2 gene and stroke susceptibility.

Conclusions: This study indicated that there was a significant association between the PITX2 gene and stroke risk, and provided some data as far as possible to support the prevention of stroke.
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http://dx.doi.org/10.1016/j.meegid.2021.105201DOI Listing
March 2022

Genetic Polymorphisms of Very Important Pharmacogene Variants in the Blang Population from Yunnan Province in China.

Pharmgenomics Pers Med 2021 17;14:1647-1660. Epub 2021 Dec 17.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, People's Republic of China.

Background: We aimed to enrich the pharmacogenomic information of a Blang population (BP) from Yunnan Province in China.

Methods: We genotyped 55 very important pharmacogene (VIP) variants from the PharmGKB database and compared their genotype distribution (GD) in a BP with that of 26 populations by the test. The minor allele frequency (MAF) distribution of seven significantly different single-nucleotide polymorphisms (SNPs) was conducted to compare the difference between the BP and 26 other populations.

Results: Compared with the GD of 55 loci in the BP, among 26 studied populations, GWD, YRI, GIH, ESN, MSL, TSI, PJL, ACB, FIN and IBS were the top-10 populations, which showed a significantly different GD >35 loci. CHB, JPT, CDX, CHS, and KHV populations had a significantly different GD <20 loci. A GD difference of 27-34 loci was found between the BP and 11 populations (LWK, CEU, ITU, STU, PUR, CLM, GBR, ASW, BEB, MXL and PEL). The GD of five loci (rs750155 (), rs4291 (), rs1051298 (), rs1131596 () and rs1051296 ()) were the most significantly different in the BP as compared with that of the other 26 populations. The genotype frequency of rs1800764 () and rs1065852 () was different in all populations except for PEL and LWK, respectively. MAFs of rs1065852 () and rs750155 () showed the largest fluctuation between the BP and SAS, EUR, AFR and AMR populations.

Conclusion: Our data can provide theoretical guidance for safe and efficacious personalized drug use in the Blang population.
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http://dx.doi.org/10.2147/PGPM.S327313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691194PMC
December 2021

C5orf66 rs4976270/rs639933 Are Associated with Colorectal Cancer Risk in Southern Chinese Han Population: A Case-Control Study.

Digestion 2022 12;103(2):103-115. Epub 2021 Oct 12.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, China.

Background: Colorectal cancer (CRC) is one of the common malignant tumors, with high mortality and poor prognosis. Our study aimed to determine the association between the long noncoding RNA (LncRNA) C5orf66 polymorphism and CRC risk in southern Chinese Han population.

Method: Using the experimental design of "case-control" study (512 cases and 513 controls), we selected 4 candidate single-nucleotide polymorphisms (SNPs) of C5orf66. All candidate SNPs were genotyped by Agena MassARRAY. Logistic regression was used to analyze the association between SNPs and CRC risk. Then, we used false-positive report probability analysis to detect whether the significant result is just a chance or noteworthy observation. Multi-factor dimensionality reduction was used to analyze the interaction of "SNP-SNP" in CRC risk.

Results: Our results showed that C5orf66 SNPs rs4976270 (odds ratio [OR] = 1.69, p = 0.021) and rs639933 (OR = 1.67, p = 0.024) were, respectively, associated with increasing CRC risk in the southern Chinese Han population. Stratified analysis showed that rs4976270 and rs639933 were significantly associated with an increased risk of CRC in subgroups (>60 years, body mass index ≤24 and drinking) under multiple genetic models. In addition, rs254563 and rs647161 also had potential association with CRC risk in subgroups (BMI ≤24 and drinking). Finally, haplotype analysis results showed that haplotype "TA" was significantly associated with increased CRC risk (OR = 1.21, confidence interval = 1.47-2.02, p = 0.043).

Conclusion: Our study provides a new idea for the risk assessment of CRC. LncRNA C5orf66 SNPs have a certain association with CRC risk in the southern Chinese Han population.
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http://dx.doi.org/10.1159/000518519DOI Listing
March 2022

Genetic analysis of pharmacogenomic VIP variants in the Wa population from Yunnan Province of China.

BMC Genom Data 2021 11 19;22(1):51. Epub 2021 Nov 19.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, China.

Background: The variation of drug responses and target does among individuals is mostly determined by genes. With the development of pharmacogenetics and pharmacogenomics, the differences in drug response between different races seem to be mainly caused by the genetic diversity of pharmacodynamics and pharmacokinetics genes. Very important pharmacogenetic (VIP) variants mean that genes or variants play important and vital roles in drug response, which have been listed in pharmacogenomics databases, such as Pharmacogenomics Knowledge Base (PharmGKB). The information of Chinese ethnic minorities such as the Wa ethnic group is scarce. This study aimed to uncover the significantly different loci in the Wa population in Yunnan Province of China from the perspective of pharmacogenomics, to provide a theoretical basis for the future medication guidance, and to ultimately achieve the best treatment in the future.

Results: In this study, we recruited 200 unrelated healthy Wa adults from the Yunnan province of China, selected 52 VIP variants from the PharmGKB for genotyping. We also compared the genotype frequency and allele distribution of VIP variants between Wa population and the other 26 populations from the 1000 Genomes Project ( http://www.1000Genomes.org/ ). Next, χ test was used to determine the significant points between these populations. The study results showed that compared with the other 26 population groups, five variants rs776746 (CYP3A5), rs4291 (ACE), rs3093105 (CYP4F2), rs1051298 (SLC19A1), and rs1065852 (CYP2D6) had higher frequencies in the Wa population. The genotype frequencies rs4291-TA, rs3093105-CA, rs1051298-AG and rs1065852-GA were higher than those of the other populations, and the allele distributions of rs4291-T and rs3093105-C were significantly different. Additionally, the difference between the Wa ethnic group and East Asian populations, such as CDX, CHB, and CHS, was the smallest.

Conclusions: Our research results show that there is a significant difference in the distribution of VIP variants between the Wa ethnic group and the other 26 populations. The study results will have an effect on supplementing the pharmacogenomics information for the Wa population and providing a theoretical basis for individualised medication for the Wa population.
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http://dx.doi.org/10.1186/s12863-021-00999-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605568PMC
November 2021

ARRDC3 polymorphisms may affect the risk of glioma in Chinese Han.

Funct Integr Genomics 2022 Feb 8;22(1):27-33. Epub 2021 Nov 8.

Department of Neurosurgery, the First Affiliated Hospital of Xi'an Jiaotong University, # 277 YanTa West Road, Xi'an, 710061, Shaanxi, China.

This study ascertained to explore the potential contribution of ARRDC3 polymorphisms in the risk and prognosis of glioma. One thousand sixty-one patients and healthy controls were conducted to assess whether ARDC3 polymorphism was associated with glioma risk and prognosis. Four sites in ARRDC3 were selected and genotyped in MassARRAY platform. The calculated odd ratios and 95% confidence intervals from logistic regression were applied for risk assessment. The relationship between ARRDC3 variants and glioma prognosis was evaluated using log-rank test, Kaplan-Meier analysis, and so on. Also, false-positive report probability (FPRP) and statistical power were also assessed. Our findings suggested the negative role of ARRDC3 polymorphisms in the glioma risk. We also found the effect of candidate SNPs in ARRDC3 on the susceptibility to glioma was dependent on the age, gender, and histology of glioma patients. The results suggested that the genetic polymorphisms of ARRDC3 were related to an increased risk of glioma.
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http://dx.doi.org/10.1007/s10142-021-00807-7DOI Listing
February 2022

Analysis of mutations in the Chinese Uyghur population.

Am J Transl Res 2021 15;13(9):10871-10881. Epub 2021 Sep 15.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University Xi'an 710069, Shaanxi, China.

Genetic characteristics of in different populations may be helpful to explore interethnic variability in drug response and disease susceptibility. There is no information about the genetic profile of in the Chinese Uyghur population. We used PCR and first-generation sequencing technology to investigate mutations in 100 unrelated healthy Chinese Uyghurs. The chi-square test was used to compare genotyping data of in the Chinese Uyghur population with other ethnic groups. The SIFT and PolyPhen-2 online tools were used to predict the protein function of the novel nonsynonymous mutations in . CADD software was used to predict pathogenicity of the mutations. We found twenty-eight mutations in , five new mutations, three alleles ( and ), and three genotypes ( and ) in the Chinese Uyghur population. The allele frequencies of and were 96%, 3.45%, and 0.5%, respectively. Interethnic comparison found that subgenotype in Uyghur was significantly higher than in Taiwanese and African Americans, and frequency in Uyghur was slightly lower than that in Taiwanese and African Americans (<0.05); *8 was only found in Chinese Uyghur and Korean populations, with frequencies of 0.5% and 0.8%, respectively. Furthermore, the protein prediction results revealed that the five nonsynonymous mutations could influence protein structure and function. The observations of this study give rise to useful information on mutations in Chinese Uyghurs, which may support future important clinical implications for the use of medications metabolized by .
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507070PMC
September 2021

Fc receptor-like 1, 3, and 6 variants are associated with rheumatoid arthritis risk in the Chinese Han population.

Genes Environ 2021 Oct 7;43(1):42. Epub 2021 Oct 7.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6 East Wenhui Road, Xianyang, 712082, Shaanxi, China.

Background: Rheumatoid arthritis (RA) is the most common autoimmune system diseases in our world. More studies in recent years have shown that FCRL gene polymorphisms is closely related to autoimmune diseases. It is suggested that genetic factors play a crucial role in the pathogenesis of this disease. In this study, we aimed to investigate the relationship between FCRL1 rs2050568, FCRL3 rs2317230 and FCRL6 rs58240276 polymorphisms and RA risk in the Chinese Han population. 506 with RA patients and 509 healthy controls were recruited in this study, and the single nucleotide polymorphisms (SNPs) was successfully genotyped using the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjusting for age and gender were conducted to assess these SNPs polymorphisms and RA risk. The multifactor dimensionality reduction (MDR) method was conducted to analyze SNP-SNP interaction.

Results: Our results revealed that there no significant association was observed between the allele and genotype frequencies among these SNPs and RA risk (all p > 0.05). Straified analysis by age and gender, the results confirmed that FCRL1 rs2050568 T/T genotype enhanced the risk of RA in females (p = 0.014). The G/T - T/T genotype of FCRL3 rs2317230 was correlated with a decreased RA risk in males (p = 0.021). We also observed that the C/T-T/T genotype of FCRL6 rs58240276 was increased the risk of RA in the group at age >  54 years (p = 0.016). In addition, FCRL1 rs2050568-TT, FCRL6 rs58240276-TT and FCRL1 rs2050568-TT, FCRL3 rs2317230-TT, FCRL6 rs58240276-TT are the best models for multi-site MDR analysis (p < 0.05), and the two best models mentioned above and classes RA have the most significant correlation.

Conclusions: Our study demonstrated that FCRL1 rs2050568, FCRL3 rs2317230, and FCRL6 rs58240276 polymorphisms were correlated with RA susceptibility in the Chinese Han population.
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http://dx.doi.org/10.1186/s41021-021-00213-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499487PMC
October 2021

Preliminary study of genome-wide association identified novel susceptibility genes for thyroid-related hormones in Chinese population.

Genes Genomics 2021 Sep 17. Epub 2021 Sep 17.

Hainan Affiliated Hospital of Hainan Medical University, #19, Xiuhua Road, Xiuying District, Haikou, 570311, Hainan, People's Republic of China.

Background: Thyroid hormones are critical regulators of metabolism, development and growth in mammals. However, the genetic association of thyroid-related hormones in the Chinese Han population is not fully understood.

Objective: We aimed to identify the genetic loci associated with circulating thyroid-related hormones concentrations in the healthy Chinese Han population.

Methods: Genotyping was performed in 124 individuals using Applied Biosystems™ Axiom™ PMDA, and 796,288 single nucleotide polymorphisms (SNPs) were available for the GWAS analysis. For replication, eleven SNPs were selected as candidate loci for genotyping by Agena MassARRAY platform in additional samples (313 subjects). The values of p < 5 × 10 suggest a suggestively significant genome-wide association with circulating thyroid-related hormones concentrations.

Results: We identified that rs11178277 (PTPRB, p = 4.88 × 10) and rs7320337 (LMO7DN-KCTD12, p = 1.22 × 10) were associated with serum FT3 level. Three SNPs (rs4850041 in LOC105373394-LINC01249: p = 3.55 × 10, rs6867291 in LINC02208: p = 2.40 × 10 and rs79508321 in WWOX: p = 3.35 × 10) were related to circulating T3 level. Rs12474167 (LOC105373394-LINC01249, p = 1.65 × 10) and rs1864553 (IWS1, p = 2.00 × 10) were associated with circulating T4 concentration. The association with TGA concentration was for rs17163542 in DISP1 (p = 3.46 × 10) and rs12601151 in NOG-C17orf67 (p = 2.72 × 10). Two genome-level significant SNPs (rs2114707 in LINC01314, p = 1.69 × 10 and rs12601151, p = 1.41 × 10) associated with serum TMA concentration were identified. Moreover, rs6083269 (CST1-CST2, p = 3.36 × 10) was a significant locus for circulating TSH level. In replication, rs12601151 in NOG-C17orf67 was still associated with serum TGA level (p = 0.012).

Conclusions: The GWAS reported 11 new suggestively significant loci associated with circulating thyroid-related hormones levels among the Chinese Han population. These findings represented suggestively biological candidates for circulating thyroid-related hormones levels and provided new insights into the mechanisms of regulating serum TGA concentration.
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http://dx.doi.org/10.1007/s13258-021-01165-1DOI Listing
September 2021

The effect of CYP7B1 polymorphisms on the risk of coronary heart disease in Hainan Han population.

BMC Med Genomics 2021 09 7;14(1):220. Epub 2021 Sep 7.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, China.

Background: Coronary heart disease (CHD) is the leading cause of human death worldwide. Genetic factors play an important role in the occurrence of CHD. Our study is designed to investigate the influence of CYP7B1 polymorphisms on CHD risk.

Methods: In this case-control study, 508 CHD patients and 510 healthy individuals were recruited to determine the correlation between CYP7B1 polymorphisms (rs7836768, rs6472155, and rs2980003) and CHD risk. The associations were evaluated by computing odds ratios (OR) and 95% confidence intervals (CI) with logistic regression analysis. The association between SNP-SNP interaction and CHD susceptibility was carried out by multifactor dimensionality reduction analyses.

Results: Our study found that rs6472155 is significantly associated with an increased risk of CHD in age > 60 years (OR 2.20, 95% CI = 1.07-4.49, p = 0.031), women (OR 3.17, 95% CI = 1.19-8.44, p = 0.021), and non-smokers (3.43, 95% CI = 1.16-10.09, p = 0.025). Rs2980003 polymorphism has a lower risk of CHD in drinkers (OR 0.47, 95% CI = 0.24-0.91, p = 0.025). Further analyses based on false-positive report probability validated these significant results. Besides, it was found that rs6472155 polymorphism was associated with uric acid level (p = 0.034).

Conclusion: Our study indicated that CYP7B1 polymorphisms are related to the risk of CHD, which provides a new perspective for prevent of CHD.
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http://dx.doi.org/10.1186/s12920-021-01067-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422734PMC
September 2021

Impacts of Variants on Breast Cancer Susceptibility in Northern Chinese Han Females: A Population-Based Case-Control Study.

J Oncol 2021 28;2021:4990695. Epub 2021 Aug 28.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China.

Background: , also known as was reported to be a -regulated long noncoding RNA (lncRNA), which played an essential role in the pathogenesis of breast cancer (BC). We aimed to observe the potential association between polymorphisms and BC risk in Northern Chinese Han females.

Methods: Totally, 555 healthy individuals and 561 patients with BC were recruited. Five candidate SNPs (rs6499221, rs3931698, rs8044565, rs3852740, and rs111577197) of were genotyped with the Agena MassARRAY system. Odds ratio (OR) and 95% confidence intervals (CIs) were applied to evaluate the relationship of genetic polymorphisms with BC susceptibility. Additionally, stratification analysis based on clinical features and haplotype analysis were also conducted. Finally, multifactor dimensionality reduction (MDR) analysis was performed to assess the SNP-SNP interaction among LOC105371267 variants, and false-positive report probability (FPRP) analysis was used to validate the result of this study.

Results: In this study, rs3931698 was a protective factor of BC in total (GG homozygote: OR = 0.30, 95% CI: 0.11-0.82, =0.018; recessive model: OR = 0.30, 95% CI: 0.11-0.84, =0.021). In stratification analysis based on the average age of 52 years and clinical characteristics (PR status, III-IV TNM stage), rs3931698 was also demonstrated to be associated with BC susceptibility. In addition, rs6499221 and rs3852740 were also associated with BC susceptibility among patients at age <52 years and patients with BC in a positive status. Thus, the haplotype analysis had a negative result for the incidence of BC ( > 0.05), and haplotype consisting of rs8044565 and rs111577197 was nonsignificantly associated with the BC risk. Finally, MDR and FPRP analyses also validated the result of this study.

Conclusion: Polymorphisms rs3931698, rs6499221, and rs3852740 of were found to be associated with the risk of BC in total, and stratification analysis in the Northern Chinese Han females suggested that variants might be helpful to predict BC progression.
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http://dx.doi.org/10.1155/2021/4990695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407995PMC
August 2021

Population Genetic Difference of Pharmacogenomic VIP Variants in the Tibetan Population.

Pharmgenomics Pers Med 2021 16;14:1027-1040. Epub 2021 Aug 16.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People's Republic of China.

Background: Genetic variation influences drug reaction or adverse prognosis. The purpose of this research was to genotype very important pharmacogenetic (VIP) variants in the Tibetan population.

Methods And Materials: Blood samples from 200 Tibetans were randomly collected and 59 VIP variants were genotyped, and then compared our data to 26 other populations in the 1000 project to further analyze and identify significant difference.

Results: The results showed that on comparing with most of the 26 populations from the 1000 project, rs4291 (), rs1051296 () and rs1065852 () significantly differed in the Tibetan population. Furthermore, three significant loci were related to drug response. In addition, the allele frequency of Tibetans least differed from that of East Asian populations, and most differed from that of Americans.

Conclusion: Three significant loci of variation rs4291, rs1051296 and rs1065852 were associated with drug response. This result will contribute to improving the information of the Tibetan in the pharmacogenomics database, and providing a theoretical basis for clinical individualised drug use in Tibetans.
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http://dx.doi.org/10.2147/PGPM.S316711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379641PMC
August 2021

Preliminary study of genome-wide association identifies novel susceptibility genes for serum mineral elements in the Chinese Han population.

Biol Trace Elem Res 2022 Jun 21;200(6):2549-2555. Epub 2021 Aug 21.

Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, #19, Xiuhua Road, Xiuying District, Haikou #19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, People's Republic of China.

Mineral elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe)) play important biological roles in enzymes, hormones, vitamins, and normal metabolism. The deficiency of mineral elements can lead to abnormal physiological functions. And some elements (such as lead (Pb)) are harmful to the body. We aim to identify genetic loci which can influence the serum levels of mineral elements (Cu, Zn, Ca, Mg, Fe, and Pb). Genotyping was performed using Applied Biosystems Axiom™ PMDA in 587 individuals, and 6,423,076 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study (GWAS) analysis. The association between genotype and phenotype was analyzed using mixed linear regression (additive genetic model) adjusting by age and gender combined with identical by descent (IBD) matrix. Genetic loci in BCHE-LOC105374194, DTX2P1-UPK3BP1-PMS2P11, VAT1L, LINC00908-LINC00683, LINC01310-NONE, and rs6747410 in VWA3B were identified to be associated with serum Cu element concentration (p < 5 × 10). ADAMTSL1 rs17229526 (p = 4.96 × 10) was significantly associated with serum Zn element levels. Genetic loci in LRP1B, PIGZ-MELTF, LINC01365-LINC02502, and HAPLN3 were related to serum Ca element levels (p < 5 ×1 0). Three SNPs in ALPK1, ASAP1-ADCY8 and IER3IP1-SKOR2 also achieved a significant association with Mg element levels (p < 5 × 10). TACSTD2-MYSM1, LRP1B, and ASAP1-ADCY8 showed suggestive associations with serum Fe element levels (p < 5 × 10). Moreover, the two most significant SNPs associated with Pb were rs304234 in CADPS-LINC00698 (p = 2.47 × 10) and rs12666460 in LOC101928211-GPR37 (p = 1.81 × 10). In summary, we reported 19 suggestive loci associated with serum mineral elements in the Chinese Han population. These findings provided new insights into the potential mechanisms regulating serum mineral elements levels.
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http://dx.doi.org/10.1007/s12011-021-02854-4DOI Listing
June 2022

CYP2C8 and CYP2E1 genetic variants increase risk of tuberculosis in northwest Chinese Han population.

Infect Genet Evol 2021 11 8;95:105022. Epub 2021 Aug 8.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China. Electronic address:

Objective: Tuberculosis (TB) is a chronic infectious disease which remains a main cause of death worldwide, and arises more and more concerns in recent years. CytochromeP450 (CYP450) is involved in the metabolism of many exogenous and endogenous compounds, and its polymorphism is associated with many diseases. The objective of our study was to explore the relationship between CYP450 polymorphisms and TB susceptibility in Northwest Chinese Han population.

Methods: 506 TB patients and 506 controls were recruited for our study, and their DNA were extracted. Six single nucleotide polymorphisms (SNPs) were selected for genotype. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated to evaluate the correlation between SNPs and TB risk.

Results: The genotype "TA" of CYP2C8 rs2275620 was related to an increased risk of TB in the co-dominant model (OR = 1.33, 95%CI =1.00-1.76, p = 0.049). In females, CYP2E1 rs2070672 was related to an increased TB susceptibility (co-dominant: OR = 1.62, 95%CI = 1.04-2.52, p = 0.032; dominant: OR = 1.66, 95%CI = 1.08-2.56, p = 0.020; additive: OR = 1.60, 95%CI = 1.08-2.36, p = 0.018), and CYP2E1 rs2515641 was also associated with an increased risk of TB (co-dominant: OR = 1.90, 95%CI = 1.19-3.04, p = 0.007; dominant: OR = 1.94, 95%CI = 1.23-3.05, p = 0.004; additive: OR = 1.80, 95%CI = 1.20-2.71, p = 0.005) in women. But there was no statistical significance between haplotypes and TB risk (p > 0.05).

Conclusions: Our research showed CYP2C8 and CYP2E1 polymorphisms are associated with an increased risk of TB in Northwest Chinese Han population, which may provide a crucial help on defining new therapeutic strategies for chemoprevention.
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http://dx.doi.org/10.1016/j.meegid.2021.105022DOI Listing
November 2021

Genetic variants of CYP4F12 gene are associated with glioma susceptibility.

Int J Cancer 2021 12 28;149(11):1910-1915. Epub 2021 Aug 28.

Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Glioma is a common and fatal primary malignant tumor of the central nervous system, and its prognosis is poor. To determine the susceptibility markers of gliomas in Chinese population we conducted a genome-wide association study (GWAS) of glioma in the Han Chinese population, with a total of 485 glioma cases and 485 controls. Genotyping was conducted using the Applied Biosystems Axiom Precision Medicine Diversity Array. Besides, we carried out imputation using IMPUTE 2.0 software, and the 1000 Genomes Phase 3 was used as the reference panel. The logistic regression model was used to analyze the association of each SNP with glioma risk, assuming an additive genetic model, which was implemented in PLINK version 1.9. Odds ratio (OR) and 95% confidence interval (CI) were estimated from logistic regression analysis with adjustment for age and gender. The results revealed that the SNP (rs688755) in the exon region of CYP4F12 at 19p13.12 reached genome-wide significance associated with gliomas (P = 2.35 × 10 , OR = 3.55, 95% CI = 2.20-5.74). Our findings provide deeper insight into the genetic contribution to glioma in different populations.
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http://dx.doi.org/10.1002/ijc.33755DOI Listing
December 2021

Network pharmacology and molecular docking analysis on mechanisms of Tibetan Hongjingtian () in the treatment of COVID-19.

J Med Microbiol 2021 Jul;70(7)

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, PR China.

Coronavirus disease 2019 (COVID-19) is a highly contagious disease and ravages the world. We proposed that might have potential value in the treatment of COVID-19 patients by regulating the immune response and inhibiting cytokine storm. We aimed to explore the potential molecular mechanism for () against the immune regulation of COVID-19, and to provide a referenced candidate Tibetan herb () to overcome COVID-19. Components and targets of were retrieved from the TCMSP database. GO analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment were built by R bioconductor package to explore the potential biological effects for targets of . The -compound-target network, target pathway network and protein-protein interaction (PPI) network were constructed using Cytoscape 3.3.0. Autodock 4.2 and Discovery Studio software were applied for molecular docking. Four bioactive components (quercetin, kaempferol, kaempferol-3-O-α-l-rhamnoside and tamarixetin) and 159 potential targets of were identified from the TCMSP database. The result of GO annotation and KEGG-pathway-enrichment analyses showed that target genes of were associated with inflammatory response and immune-related signalling pathways, especially IL-17 signalling pathway, and TNF signalling pathway. Targets-pathway network and PPI network showed that IL-6, IL-1B and TNF-α were considered to be hub genes. Molecular docking showed that core compound (quercetin) had a certain affinity with IL-1β, IL-6 and TNF-α. might play an anti-inflammatory and immunoregulatory role in the cytokine storm of COVID-19.
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http://dx.doi.org/10.1099/jmm.0.001374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493420PMC
July 2021

The association study between CYP20A1, CYP4F2, CYP2D6 gene polymorphisms and coronary heart disease risk in the Han population in southern China.

Genes Genomics 2021 Jul 24. Epub 2021 Jul 24.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, China.

Background: Coronary heart disease (CHD) is a disease that seriously harms human health. Genetic factors seriously affect the CHD susceptibility. The CYP20A1, CYP4F2 and CYP2D6 are important drug metabolism enzymes in the human body.

Objective: We aimed to explore the association between CYP20A1, CYP4F2, CYP2D6 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese Southern Han population.

Methods: Based on the 'case-control' experimental design (505 cases and 508 controls), we conducted an association study between 5 candidate SNPs selected from CYP20A1 (rs2043449), CYP4F2 (rs2108622, rs3093106, rs309310), CYP2D6 (rs1065852) and CHD risk. Logistic regression was used to analyze the CHD susceptibility under different genetic models. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction of 'SNP-SNP' in CHD risk.

Results: Our results showed that under multiple genetic models, CYP2D6 rs1065852 significantly increased the CHD risk in these participants who are ≤ 60 years old (OR 1.40, CI 1.07-1.82, p = 0.013), smokers (OR 1.40, CI 1.02-1.93, p = 0.039), or have family history (OR 1.24, CI 1.02-1.51, p = 0.035). CYP4F2 SNPs rs2108622 (OR 0.63, CI 0.43-0.93, p = 0.020), rs3093106 (OR 0.52, CI 0.29-0.92, p = 0.023), and rs309310 (OR 0.55, CI 0.31-0.96, p = 0.033) were potentially associated with the course of CHD patients.

Conclusion: Our study found that CY2D6 rs1065852 has an outstanding and significant association with increased CHD risk. Our study provided data supplements for CHD genetic susceptibility loci, and also provided a new and valuable reference for CHD drug treatment.
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http://dx.doi.org/10.1007/s13258-021-01125-9DOI Listing
July 2021

Impact of COL6A4P2 gene polymorphisms on the risk of lung cancer: A case-control study.

PLoS One 2021 21;16(5):e0252082. Epub 2021 May 21.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China.

Lung cancer (LC) is a malignant tumor that poses the greatest threat to human health and life. Most studies suggested that the occurrence of LC is associated with environmental and genetic factors. We aimed to explore the association between COL6A4P2 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese Southern Han population. Based on the 'case-control' experimental design (510 cases and 495 controls), we conducted an association study between five candidate COL6A4P2 SNPs and the corresponding LC risk. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression to analyze the LC susceptibility under different genetic models. The results showed that COL6A4P2 rs34445363 was significantly associated with LC risk under alleles model (OR = 1.26, 95%CI: 1.01-1.58, p = 0.038). In addition, rs34445363 was also significantly associated with LC risk under the log-additive model (OR = 1.26, 95%CI: 1.01-1.58, p = 0.041). The results of subgroup analysis showed that rs34445363 (OR = 1.42, 95%CI: 1.03-1.95, p = 0.033) and rs61733464 (OR = 0.72, 95%CI: 0.52-0.99, p = 0.048) were both significantly associated with LC risk in the log-additive model among participants who were ≤ 61 years old. We also found that the variation of rs34445363 (GA vs. GG, OR = 1.73, 95%CI: 1.04-2.86, p = 0.034) and rs77941834 (TA vs. TT, OR = 1.88, 95%CI: 1.06-3.34, p = 0.032) were associated with LC risk in the codominant model among female participants. Our study is the first to find that COL6A4P2 gene polymorphism is associated with LC risk in the Chinese Han population. Our study provides a basic reference for individualized LC prevention.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252082PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139505PMC
October 2021

Genetic Variants Are Associated with the Susceptibility to Cervical Cancer in a Chinese Population.

Biomed Res Int 2021 20;2021:6670456. Epub 2021 Mar 20.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082 Shaanxi, China.

Background: Cervical cancer (CC) is the second most common tumor in women worldwide. Studies have been accepted that genetic variations play an important role in the development of CC. The aim of this study was to evaluate the impact of variants on CC risk.

Methods: 508 patients of cervical cancer and 497 healthy subjects were recruited to determine the impact of polymorphisms on CC susceptibility. The associations were investigated by computing odds ratios (ORs) and 95% confidence intervals. The effect of SNP-SNP interactions on CC risk was explored by multifactor dimensionality reduction analysis.

Results: Our study showed that rs11904127 (OR 0.79, = 0.010) and rs62162674 (OR 0.82, = 0.044) of significantly decreased cervical cancer risk. Stratified analysis indicated that rs11904127 and rs62162674 present decreased susceptibility to CC in age > 51 years (OR 0.74, = 0.019; OR 0.72, = 0.014, respectively). Haplotype analyses revealed that GTC has a lower risk to cervical cancer (OR = 0.43, = 0.018). Besides, there is strong interaction of rs11904127 and rs2366264.

Conclusion: Rs11904127 and rs62162674 in are related to cervical cancer. We suggest that these variants can be used as prognostic markers for judging the susceptibility to cervical cancer.
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http://dx.doi.org/10.1155/2021/6670456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007361PMC
May 2021

The Influence of NDRG1 Single Nucleotide Polymorphisms on Glioma Risk and Prognosis in Chinese Han Population.

Cell Mol Neurobiol 2022 Aug 12;42(6):1949-1964. Epub 2021 Mar 12.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, China.

Glioma is a highly fatal malignant tumor with a high recurrence rate, poor clinical treatment effect, and prognosis. We aimed to determine the association between single nucleotide polymorphisms (SNPs) of NDRG1 and glioma risk and prognosis in the Chinese Han population. 5 candidate SNPs were genotyped by Agena MassARRAY in 558 cases and 503 controls; logistic regression was used to analyze the relationship between SNPs and glioma risk. We used multi-factor dimensionality reduction to analyze the interaction of 'SNP-SNP'; the prognosis analysis was performed by log-rank test, Kaplan-Meier analysis, and Cox regression model. Our results showed that the polymorphisms of rs3808599 was associated with the reduction of glioma risk in all participants (OR 0.41, p = 0.024) and the participants ≤ 40 years old (OR 0.30, p = 0.020). rs3802251 may reduce glioma risk in all participants (OR 0.79, p = 0.008), the male participants (OR 0.68, p = 0.033), and astrocytoma patients (OR 0.81, p = 0.023). rs3779941 was associated with poor glioma prognosis in all participants (HR = 2.59, p = 0.039) or astrocytoma patients (HR = 2.63, p = 0.038). We also found that the key factors for glioma prognosis may include surgical operation, radiotherapy, and chemotherapy. This study is the first to find that NDRG1 gene polymorphisms may have a certain association with glioma risk or prognosis in the Chinese Han population.
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http://dx.doi.org/10.1007/s10571-021-01075-6DOI Listing
August 2022

Impact of genetic variants in IL-2RA and IL-2RB on breast cancer risk in Chinese Han women.

Biochem Genet 2021 Jun 28;59(3):697-713. Epub 2021 Jan 28.

Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University, #229 North TaiBai Road, Xi'an, Shaanxi, 710069, China.

The expression of IL-2RA and IL-2RB was correlated with breast cancer (BC) progression. However, there is no literature investigating the association of IL-2RA and IL-2RB polymorphisms with BC predisposition among Chinese Han Women. Seven SNPs in IL-2RA and IL-2RB were genotyped by Agena MassARRAY platform among 553 BC patients and 550 healthy controls. Odds ratios (OR) and 95% confidence interval (CI) adjusted for age were calculated for the effect of IL-2RA and IL-2RB variants on BC susceptibility. IL-2RA rs12722498 was a protective factor for BC occurrence (OR = 0.70, p = 0.019), especially in subjects with age ≤ 52 years (OR = 0.55, p = 0.004). IL-2RA rs12569923 (OR = 9.07, p = 0.033), IL-2RB rs2281089 (OR = 0.67, p = 0.043) and rs9607418 (OR = 0.59, p = 0.012) were related to the incidence of estrogen receptor positive (ER +) BC. IL-2RB rs3218264 (OR = 1.38, p = 0.010) and rs9607418 (OR = 0.56, p = 0.009) were associated with the risk of developing progesterone receptor positive (PR +) BC. Rs2281089 (OR = 1.54, p = 0.012) and rs1573673 (OR = 0.72, p = 0.035) were correlated to Ki-67 level. Moreover, IL-2RB rs2281089 (OR = 0.72, p = 0.022) showed a reduced risk of BC metastasis, and IL-2RA rs12722498 (OR = 0.54, p = 0.030) had a lower frequency in BC patients with tumor size > 2 cm. Our study identified the potential effect of genetic variations in IL-2RA and IL-2RB on BC susceptibility and/or BC clinicopathologic indicators among Chinese Han Women.
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http://dx.doi.org/10.1007/s10528-021-10029-yDOI Listing
June 2021

Influence of CMTM8 polymorphisms on lung cancer susceptibility in the Chinese Han population.

Pharmacogenet Genomics 2021 06;31(4):89-95

Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University.

Background: Lung cancer is the leading cause of cancer-related mortality worldwide and CMTM8 is a potential tumor suppressor gene, which is down-regulated in lung cancer. The objective of this research was to assess the association of CMTM8 genetic polymorphisms with lung cancer risk.

Methods: To evaluate the correlation between CMTM8 polymorphisms and lung cancer risk, Agena MassArray platform was used for genotype determination among 509 lung cancer patients and 506 controls. Multiple genetic models, stratification analysis and Haploview analysis were used by calculating odds ratio (OR) and 95% confidence intervals (CIs).

Results: Significant associations were detected between CMTM8 rs6771238 and an increased lung cancer risk in codominant (adjusted OR = 1.57, 95% CI: 1.01-2.42, P = 0.044) and dominant (adjusted OR = 1.54, 95% CI: 1.01-2.36, P = 0.047) models. After sex stratification analysis, we observed that rs6771238 was related to an increased risk of lung squamous cell carcinoma, while rs6771238 was associated with an increased risk of lung adenocarcinoma. Rs9835916 was linked to increased risk of lymph node metastasis in lung cancer patients.

Conclusion: Our study first reported that CMTM8 polymorphisms were a risk factor for lung cancer, which suggested the potential roles of CMTM8 in the development of lung cancer.
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http://dx.doi.org/10.1097/FPC.0000000000000426DOI Listing
June 2021

Impact of ESR1 Polymorphisms on Risk of Breast Cancer in the Chinese Han Population.

Clin Breast Cancer 2021 06 16;21(3):e235-e242. Epub 2020 Oct 16.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China. Electronic address:

Background: The estrogen receptor-1 (ESR1) gene encodes estrogen receptor-α, which is a major biomarker in the development of breast cancer. This study aimed to investigate the effect of ESR1 polymorphisms on breast cancer in Chinese Han women.

Materials And Methods: We genotyped 4 candidate single nucleotide polymorphisms (SNPs) in ESR1 among 503 patients with breast cancer and 503 healthy people using the Agena MassARRAY platform. The association between ESR1 polymorphisms and breast cancer risk was evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) under 4 genetic models. The HaploReg v4.1 and GEPIA database were used for SNP functional annotation and ESR1 expression analysis, respectively.

Results: The T allele of rs9383938 in ESR1 was significantly associated with an increased breast cancer risk (OR, 1.26; 95% CI, 1.05-1.50; P = .013). In genetic models, rs9383938 increased breast cancer risk in the codominant model (OR, 1.54; 95% CI, 1.07-2.22; P = .021), the dominant model (OR, 1.31; 95% CI, 1.01-1.68; P = .040), and the additive model (OR, 1.24; 95% CI, 1.04-1.48; P = .017). Stratification analysis showed that rs9383938 and rs2228480 raised the breast cancer susceptibility in individuals aged younger than 52 years old. Rs1801132 of ESR1 was significantly associated with the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 in the allele model and genetic models (P < .05).

Conclusions: This study demonstrated that ESR1 polymorphisms might influence breast cancer susceptibility in the Chinese Han population. Further mechanism studies are needed to confirm the contribution of ESR1.
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http://dx.doi.org/10.1016/j.clbc.2020.10.003DOI Listing
June 2021

Assessment of ADCY9 polymorphisms and colorectal cancer risk in the Chinese Han population.

J Gene Med 2021 02 15;23(2):e3298. Epub 2021 Jan 15.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China.

Background: Recently, ADCY9 has been found to be highly expressed in colon cancer, and high ADCY9 expressionis a poor prognostic factor of colon cancer. However, no study has reported on the relationship between single nucleotide polymorphisms (SNPs) of ADCY9 and colorectal cancer risk in the Chinese Han population.

Methods: To evaluate the association between four ADCY9 SNPs and colorectal cancer risk, we performed a case-control study including 511 colorectal cancer patients and 511 healthy controls. SNPs were genotyped using the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA). The distributions of alleles and genotypes frequencies between the case and control groups were compared using chi-squared. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression adjusted for age and gender to assess the association between SNPs and colorectal cancer risk.

Results: The overall analysis found that rs2230742 was associated with an increased risk of colorectal cancer (AA versus GG: OR = 3.54, 95% CI = 1.16-10.86, p = 0.027; recessive model: OR = 3.55, 95% CI = 1.16-10.85, p = 0.027). Stratification analysis showed that rs2230742 was associated with an increased rectal cancer risk; rs11076810 was associated with a reduced colorectal cancer risk for age > 59 years. No association was observed between other two SNPs and colorectal cancer risk.

Conclusions: Our findings suggest that ADCY9 polymorphisms (rs2230742 and rs11076810) have an effect on colorectal cancer risk in the Chinese Han population. Future association and functional studies are required to confirm our findings and explore the mechanism of ADCY2 in colorectal cancer.
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http://dx.doi.org/10.1002/jgm.3298DOI Listing
February 2021

CYP24A1 rs1570669 Variant Has a Protective Effect against Tumors of the Urinary System.

Public Health Genomics 2020 28;23(5-6):200-209. Epub 2020 Oct 28.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, China,

Background: Common malignant tumors of the urinary system include renal cell carcinoma, bladder carcinoma, and prostate cancer. The research on the CYP24A1 gene for prostate cancer is mainly concentrated in European and American populations, and there are few studies in the Chinese population. Therefore, we selected bladder cancer, prostate cancer, and renal cancer as the research objects to explore the influence of CYP24A1 on the genetic susceptibility of urinary system tumors.

Materials And Methods: rs6068816, rs2296241, rs2762934, and rs1570669 in 529 patients and 523 controls were genotyped via the Agena MassARRAY. Logistic regression analysis was used to evaluate the odd ratios (ORs) and 95% confidence intervals (CIs) of two SNPs with susceptibility of urinary system cancer. Database predicts the expression of the CYP24A1 gene in urinary system cancer.

Results: Individuals with the AG genotype of CYP24A1 rs1570669 has a 28% lower risk of developing urinary system tumors (OR = 0.72, 95% CI: 0.56-1.13, p = 0.016) and has a 31% lower risk of developing renal cancer (OR = 0.69, 95% CI: 0.51-0.92, p = 0.012).

Conclusions: CYP24A1 rs1570669 may play an important role in the susceptibility of tumors of the urinary system and renal cancer.
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http://dx.doi.org/10.1159/000509190DOI Listing
May 2021

Variants in multiple genes are associated with esophageal cancer risk in a Chinese Han population: A case-control study.

J Gene Med 2020 12 10;22(12):e3266. Epub 2020 Sep 10.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, China.

Background: The present study investigated whether 16 single nucleotide polymorphisms (SNPs), selected based on minor allele frequencies, Hardy-Weinberg equilibrium and reported SNPs related to the susceptibility of certain gastrointestinal cancer, were associated with esophageal cancer (EC) risk in a Chinese Han population.

Methods: We genotyped 16 SNPs among 506 cases and 507 controls using Agena MassARRAY (Agena, San Diego, CA, USA). The association between 16 SNPs and EC risk was analyzed by a chi-squared test and genetic model analysis. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: rs1050631 and the rs6214 were associated with a decreased EC risk (OR = 0.75, p = 0.038; OR = 0.74, p = 0.045, respectively). In stratification analysis, the rs9868873 was associated with an increased EC risk (age < 64 years) (OR = 5.03, p = 0.005). The rs6214 was associated with a decreased EC risk (age < 64 years) (OR = 0.59, p = 0.025). The rs861530 was significantly associated with a decreased EC risk (age ≥ 64 years) (OR = 0.67, p = 0.046). rs1050631 was associated with a decreased EC risk in males (OR = 0.71, p = 0.034). In the stratified analysis of clinical stage III/IV, the rs1800566 was associated with a decreased EC risk (OR = 0.49, p = 0.024). Finally, the rs1052133 was associated with an elevated EC risk in the stratified analysis of lymph node metastasis (OR = 1.73, p = 0.025).

Conclusions: The findings of the present study demonstrate that SLC39A6, IGF1, SEMA5B, XRCC3, NQO1 and OGG1 polymorphisms were associated with EC risk under multiple models.
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http://dx.doi.org/10.1002/jgm.3266DOI Listing
December 2020
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