Publications by authors named "Yulu Gu"

23 Publications

  • Page 1 of 1

Association between urbanisation and the risk of hyperuricaemia among Chinese adults: a cross-sectional study from the China Health and Nutrition Survey (CHNS).

BMJ Open 2021 Mar 10;11(3):e044905. Epub 2021 Mar 10.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China

Objective: To explore the association between urbanicity and hyperuricaemia (HUA) and whether urbanicity is an independent risk factor for HUA in Chinese adults.

Design: Data analysis from a cross-sectional survey.

Setting And Participants: 8579 subjects aged 18 years or older were enrolled in the study from the 2009 wave of the China Health and Nutrition Survey to analyse the association between urbanicity and HUA. We divided them into three categories according to urbanisation index (low, medium and highly urbanised groups).

Main Outcome Measures: HUA was defined as serum uric acid ≥7 mg/dL in men and ≥6 mg/dL in women.

Results: The prevalence of HUA in low, medium and highly urbanised groups was 12.2%, 14.6% and 19.8%, respectively. The independent factors influencing serum uric acid included age, gender, hypertension, diabetes, chronic kidney disease, drinking, obesity and community-level urbanisation index (β=0.016, p<0.001). The risk of HUA in the highly urbanised group was significantly higher than that of the low urbanised group (OR 1.771, 95% CI 1.545 to 2.029, p<0.001), even after adjusting for other covariates (OR 1.661, 95% CI 1.246 to 2.212, p=0.001). In a subgroup analysis, we found that age, gender, comorbidity (such as hypertension, diabetes, obesity and chronic kidney disease) and physical activity affected the association between urbanisation and the risk of HUA.

Conclusions: Our findings suggest that living in highly urbanised areas is linked with higher risk of HUA independent of cardiometabolic and health-related behavioural risk factors, which have been shown to increase along with urbanisation.
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http://dx.doi.org/10.1136/bmjopen-2020-044905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949434PMC
March 2021

Novel predictive biomarkers for acute injury superimposed on chronic kidney disease.

Nefrologia 2021 Mar-Apr;41(2):165-173. Epub 2020 Nov 4.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Medical Center of Kidney, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China. Electronic address:

Introduction And Objectives: Chronic kidney disease (CKD) is a risk factor for the development of acute kidney injury (AKI). Recent studies have revealed numerous biomarkers eligible for AKI prediction. However, the expression and performance of AKI biomarkers in acute injury superimposed on preexisting CKD (AonC) remain elusive. The aim of this study was to evaluate whether biomarkers which robustly expressed in acute kidney injury could predict acute injury based on CKD.

Materials And Methods: Mice were classified into cohorts: AKI, CKD, AonC and sham. The AonC model mice were subjected to renal bilateral ischemia/reperfusion (I/R) injury fourteen days after intraperitoneally administrated with 20mg/kg aristolochic acid. Severity of acute ischemic injury was stratified by clamping the dissected bilateral renal arteries with non-traumatic microvascular clips for 20 or 35min. The AKI mice were induced with renal bilateral I/R injury and CKD mice were crafted with 20mg/kg aristolochic acid administrated intraperitoneally. Histology, genetic and protein expression of biomarkers were measured in three cohorts.

Results: We found that serum creatinine dramatically increased in severe (sAonC) but not in moderate (mAonC) injury mice. Upregulation of Kidney injury molecule-1 (KIM-1) mRNA, tissue inhibitor of metalloproteinase-2 (TIMP-2), Syndecan-1 (SDC-1) mRNA and insulin-like growth factor binding protein-7 (IGFBP7) protein indicated the onset of mAonC. An increase in neutrophil gelatinase-associated lipocalin (NGAL), rhomboid-like protein 2 (RHBDL2), Syndecan-1 (SDC-1) mRNA and protein, and a decrease in IGFBP7 protein were associated with sAonC.

Conclusions: Our study revealed the variational expression of AKI biomarkers in AonC kidneys, and uncovered IGFBP7 protein can be used as a sensitive biomarker to predict and differentiate AonC severity. The performance of RHBDL2 and SDC-1 in predicting severe AonC was promising, providing new biomarkers for predicting AonC.
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http://dx.doi.org/10.1016/j.nefro.2020.06.007DOI Listing
November 2020

Hydrogen sulfide attenuates renal fibrosis by inducing TET-dependent DNA demethylation on Klotho promoter.

FASEB J 2020 09 30;34(9):11474-11487. Epub 2020 Jul 30.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Hypoxia is a key pathogenetic characteristic of chronic kidney disease (CKD). Klotho has renoprotective effect and its expression is commonly suppressed in CKD patients. We showed that chronic hypoxia in unilateral ureteral obstruction model mice is associated with renal Klotho promoter methylation and expression silencing. Administration of low-dose of sodium hydrosulfide (NaHS) effectively ameliorated renal tubulointerstitial fibrosis in the mouse model by demethylating Klotho promoter and restoring its expression. Mechanistically, hypoxia microenvironment in CKD reduced cellular oxygen availability and Fe concentration, and led to impaired activity of ten-eleven translocation (TET), which is critical in maintaining Klotho promoter demethylation status. NaHS treatment greatly improved hypoxia condition, restored TET activity, reversed DNA methylation, and thus, increased Klotho expression. Our results strongly suggested that correcting hypoxia condition to restore TET activity could be a promising therapeutic strategy against CKD.
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http://dx.doi.org/10.1096/fj.201902957RRDOI Listing
September 2020

ε2 allele and ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) may confer the association of APOE genetic polymorphism with risks of nephropathy in type 2 diabetes: a meta-analysis.

Lipids Health Dis 2020 Jun 13;19(1):136. Epub 2020 Jun 13.

Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.

Background: Diabetic nephropathy (DN) contributes to end-stage renal failure. Microvascular injury resulted from reactive oxygen species is implicated in the pathogenesis of DN. Genetic polymorphism of Apolipoprotein E (APOE) influences the antioxidative properties of the protein. The relationship of APOE polymorphism with the risks of nephropathy in type 2 diabetes (T2DN) remains elusive.

Methods: An up-to-date meta-analysis was conducted on the basis of studies selected from PubMed, WanFang database, Embase, Vip database, Web of Science, Scopus, and CNKI database.

Results: A total of 33 studies conferring 3266 cases and 3259 controls were selected on the basis of criteria of inclusion and exclusion in this meta-analysis. For APOE alleles, the pooled odds ratio (OR) of ε2 vs. ε3 was 1.89 (95% confidence intervals [95% CI]: 1.49-2.38, P < 0.0001). With regard to APOE genotypes, ε2/ε2, ε2/ε3, and ε2/ε4 increased the risk of T2DN (ε2/ε2 vs. ε3/ε3: OR = 2.32, 95% CI: 1.52-3.56, P = 0.0001; ε2/ε3 vs. ε3/ε3: OR = 1.97, 95% CI: 1.50-2.59, P<0.0001; ε2/ε4 vs. ε3/ε3: OR = 1.69, 95% CI: 1.18-2.44, P = 0.0046).

Conclusions: This meta-analysis found that the APOE ε2 allele and the ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) are the risk factors of T2DN.
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http://dx.doi.org/10.1186/s12944-020-01307-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293775PMC
June 2020

Association between exposure to the Chinese famine during early life and the risk of chronic kidney disease in adulthood.

Environ Res 2020 05 29;184:109312. Epub 2020 Feb 29.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Medical Center of Kidney Disease, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China. Electronic address:

Background And Objectives: Famine exposure in human early life is proven to be associated with urinary protein concentration and renal function but has not been studied with chronic kidney disease. We aimed to explore the association between exposure to the Chinese famine (from 1959 to 1962) in early life and the risk of chronic kidney disease in adulthood.

Design, Setting, Participants, And Measurements: We selected 6267 participants from the baseline survey of China Health and Retirement Longitudinal Study (CHARLS) 2011-2012. Based on the birth year, they were divided into fetal exposed, preschool exposed, school-aged exposed, and non-exposed groups. The estimated glomerular filtration rate (eGFR) was calculated according to Japanese coefficient-modified Chronic Kidney Disease Epidemiology Collaboration equation. Chronic kidney disease (CKD) was defined as eGFR less than 60 mL/min per 1.73 m.

Results: The prevalence of CKD in fetal exposed, preschool exposed, school-aged exposed and non-exposed groups was 4.27%, 5.41%, 9.65% and 2.42%, respectively. The risk of CKD in fetal exposed, preschool exposed and school-aged exposed groups was significantly higher than the non-exposed group. In addition, after stratification by gender and famine severity, we found that only fetal exposure to the severe famine was associated with the elevated risk of CKD among male adults (OR 4.44, 95%CI 1.10-17.92, P < 0.05), even after adjusting for age, marital status, household per capita income, history of kidney disease, hypertension, diabetes or abnormal glucose tolerance, smoking, drinking, rural/urban residence and highest educational attainment of parents.

Conclusions: Severe famine exposure as a fetus might increase the risk of chronic kidney disease in male adults.
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http://dx.doi.org/10.1016/j.envres.2020.109312DOI Listing
May 2020

Association of rs944289, rs965513, and rs1443434 in TITF1/TITF2 with Risks of Papillary Thyroid Carcinoma and with Nodular Goiter in Northern Chinese Han Populations.

Int J Endocrinol 2020 11;2020:4539747. Epub 2020 Feb 11.

Department of Cardiovascular Center, First Hospital of Jilin University, Changchun 130021, China.

Objective: In this study, we aimed to investigate the associations of three single-nucleotide polymorphisms (SNPs) on TITF1/TITF2 (rs944289, rs965513, and rs1443434) with susceptibility to papillary thyroid carcinoma (PTC) and with nodular goiter (NG) in northern Chinese Han populations.

Methods: We performed a case-control study comprising 861 PTC patients, 562 NG patients, and 896 normal controls (NCs). One TITF1 SNP (rs944289) and two TITF2 SNPs (rs965513 and rs1443434) were genotyped. Departures from Hardy-Weinberg equilibrium (HWE) in the control group were evaluated using chi-square test. Associations of the SNPs with PTC and with NG were assessed by unconditional logistic regression using the online SNPStats program. Bonferroni correction was performed for multiple tests in genotype analyses. Data analysis was performed by SPSS24.0 unless otherwise specified.

Results: For rs944289, T allele was associated with increased risks for both PTC (OR = 1.23, 95% CI: 1.08-1.41, =0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, =0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, =0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, =0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, =0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, =0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, =0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, =0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50.

Conclusions: There are associations of rs944289 and rs1443434 polymorphisms with PTC risk and association of rs944289 polymorphism with NG risk. Haplotypes T-G-G and T-G-T are risk haplotypes of PTC and NG, respectively.
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http://dx.doi.org/10.1155/2020/4539747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036112PMC
February 2020

Prevalence of autism spectrum disorder in Asia: A systematic review and meta-analysis.

Psychiatry Res 2020 02 5;284:112679. Epub 2019 Nov 5.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin 130021, China. Electronic address:

There has been an increased prevalence of the diagnosis of Autism Spectrum Disorder (ASD) globally during the last decade. An updated and overall estimate of ASD prevalence in Asia would assist health professionals to develop relevant public health strategies. We performed a systematic review by searching English databases (Medline, Embase, Web of Science, and Cochran Library) from inception date to August 6, 2018. Subgroup, sensitivity, and meta-regression analyses were performed to address heterogeneity. Publication bias was evaluated using Egger's test. A total of 2,195,497 subjects in Asia from 12 eligible studies were included in this meta-analysis. The pooled estimate of ASD prevalence among the included subjects was 0.36% (95% CI: 0.16-0.79%). The pooled ASD prevalence in males (0.45%, 95% CI: 0.19-1.04%) was higher than that in females (0.18%, 95% CI: 0.079-0.49%). ASD prevalence in East Asia, South Asia, and West Asia was 0.51% (95% CI: 0.06-4.22%), 0.31% (95% CI: 0.14-0.65%), and 0.35% (95% CI: 0.07-1.80%) respectively. The prevalence of ASD is increasing in Asia. Universal and standardized diagnostic processes for ASD should be adopted for the prevention and control programs of ASD in future.
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http://dx.doi.org/10.1016/j.psychres.2019.112679DOI Listing
February 2020

METTL14-dependent m6A regulates vascular calcification induced by indoxyl sulfate.

Life Sci 2019 Dec 4;239:117034. Epub 2019 Nov 4.

Department of Nephrology, Zhongshan Hospital, Fudan University, China; Shanghai Medical Center of Kidney, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Hemodialysis quality control center of Shanghai, China. Electronic address:

Aims: Although the functional importance of N6-methyladenosine (m6A) in various fundamental bioprocesses are well known, its effect on vascular calcification is not well studied. We investigated the role of methyltransferase-like 14 (METTL14), an m6A methylase, in vascular calcification.

Main Methods: We used clinical human samples as well as rat models and primary human artery smooth muscle cell (HASMC) cultures to study the functional role of m6A and METTL14 in vascular calcification and in HASMCs. We modulated the expression of METTL14 using siRNAs (in vitro) to study its function in regulating HASMCs m6A, osteoblasts induced by indoxyl sulfate. We performed the MeRIP-qPCR assays to map and validate m6A in individual transcripts, controls, and calcific HASMCs.

Key Findings: We discovered that the METTL14 expression increases in calcific arteries and in HASMCs induced by indoxyl sulfate, thereby increasing the m6A level in RNA and decreasing the vascular repair function. Decreasing the expression of METTL14 in calcified arteries attenuated the indoxyl sulfate-induced increase in m6A and decrease in HASMCs calcification. We performed the methylation activity of METTL14, which selectively methylates vascular osteogenic transcripts, thereby promoting their degradation and improving their protein expression induced by indoxyl sulfate. Moreover, we demonstrated that the METTL14 de-expression in HASMCs models of calcification decreased the calcification and enhanced the vascular repair function.

Significance: Collectively, our results demonstrated the functional importance of METTL14-dependent vascular m6A methylome in vascular functions during calcification and provided a novel mechanistic insight to the therapeutic mechanisms of METTL14.
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http://dx.doi.org/10.1016/j.lfs.2019.117034DOI Listing
December 2019

Social-biological influences on sleep duration among adult residents of Northeastern China.

Health Qual Life Outcomes 2019 Mar 15;17(1):47. Epub 2019 Mar 15.

Cardiovascular Center, The First Hospital of Jilin University, Changchun, 130021, China.

Background: Cold climates traditionally have conferred long sleep duration in the residents in northeast China; however, modern lifestyle reduces sleep duration. In this study, we investigated social-biological factors influencing sleep duration in the adult residents in northeast China.

Methods: This study was performed using data from the Investigation of Chronic Disease Morbidity Rate and Risk Factors of Adults in Jilin Province, China. Associations between sleep duration and indices of demographic characteristics, health-related behaviors, and disease history in adult residents were analyzed using univariate analysis and multivariate logistic regression analysis.

Results: The mean sleep duration was 7.24 h. Of the 21,435 participants, approximately 53.4% had short sleep duration (sleep duration per day < 7 h), and 10.5% had long sleep duration (sleep duration per day > 9 h). There were associations between short sleep duration and indices, including age, place of residence, marital status, educational level, alcohol drinking, dietary, obesity, and history of coronary heart disease (CHD) or myocardial infarction (MI). There existed associations of long sleep duration with indices, such as age, place of residence, occupation, educational level, average monthly earnings, and physical exercise.

Conclusion: Short sleep duration is common among residents in northeast China. Age, place of residence, and educational level are implicated in both short sleep duration and long sleep duration. Short sleep duration inclines to link with the indices (marital status, alcohol drinking, dietary, obesity, and history of CHD or MI). However, long sleep duration is relevant to the indices (occupation, average monthly earnings, and physical exercise).
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http://dx.doi.org/10.1186/s12955-019-1111-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419849PMC
March 2019

Amelioration of Uremic Toxin Indoxyl Sulfate-Induced Osteoblastic Calcification by SET Domain Containing Lysine Methyltransferase 7/9 Protein.

Nephron 2019 15;141(4):287-294. Epub 2019 Feb 15.

Department of Nephrology, Zhongshan Hospital, University of Fudan, Shanghai, China.

Background: Vascular calcification (VC) is a very common phenomenon in patients with chronic kidney disease (CKD). It has been reported that some histone methylation play a role in VC as an epigenetic regulator. Indoxyl sulfate (IS) is a protein-bound uremic toxin that has been proven as one of the major risk factors of cardiovascular disease in CKD. SET domain containing lysine methyltransferase 7/9 (SET7/9) is one of the important histone methyltransferases.

Objectives: This study aimed to determine the effect of IS on the expression of SET7/9 and the role of SET7/9 in IS-induced osteoblastic differentiation and calcification of vascular smooth muscle cells (VSMCs).

Methods: VSMCs were incubated with various concentrations of IS for different durations to assess osteoblastic differentiation and expression of SET7/9. Western blot analysis and quantitative real-time polymerase chain reaction were performed to assess the protein and mRNA levels of SET7/9 respectively. The calcium content was measured to evaluate calcification.

Results: Osteoblastic differentiation and calcification of VSMCs and downregulation of the expression of SET7/9 were observed after IS treatment. The autophagy was activated after treatment with IS, whereas the inhibition of the autophagy partially attenuated the effect of IS on both the stimulation of the expression of runt-related transcription factor 2 and calcium deposition.

Conclusions: Our data demonstrated that SET7/9 downregulation and autophagy activation may be the key mechanism of IS-induced VC in CKD.
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http://dx.doi.org/10.1159/000495885DOI Listing
December 2019

SHANK1 polymorphisms and SNP-SNP interactions among SHANK family: A possible cue for recognition to autism spectrum disorder in infant age.

Autism Res 2019 03 10;12(3):375-383. Epub 2019 Jan 10.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin, China.

Autism spectrum disorder (ASD) is a serious lifelong neurodevelopmental disorder. ASD is diagnosed for children at the age of two. ASD diagnosis, as early as possible, lays the foundation for treatment and much better prognosis. Notably, gene-based test is an inherent method to recognize the potential infants with ASD before the age of two. To investigate whether SHANK family contributes to ASD prediction, on the basis of our previous studies of SHANK2 and SHANK3, we further investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. We enrolled 470 subjects (229 cases and 241 healthy controls) who were northeast Chinese Han. Four tag SNPs (rs73042561, rs3745521, rs4801846, and rs12461427) of SHANK1 were selected and genotyped. We used the SNPStats online analysis program to assess the associations between the four SNPs and ASD risk. The SNP-SNP interactions among SHANK family were analyzed using multifactor dimensionality reduction method. We found that the four SHANK1 SNPs were not associated with ASD risk in northeast Chinese Han population. There existed a strong synergistic interaction between rs11236697 [SHANK2] and rs74336682 [SHANK2], and moderate synergistic interactions (rs74336682 [SHANK2]-rs73042561 [SHANK1], rs11236697 [SHANK2]-rs77716438 [SHANK2], and rs11236697 [SHANK2]-rs75357229 [SHANK2]). These SHANK1 variants may not affect the susceptibility to ASD in Chinese Han population. SNP-SNP interactions in SHANK family may confer ASD risk. Autism Res 2019, 12: 375-383 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: ASD is a serious lifelong neurodevelopmental disorder with strong genetic components. We investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. Our results indicated that there exists no association between SHANK1 SNPs and ASD, and SNP-SNP interactions in SHANK family may confer ASD risk in the Northeast Han Chinese population. Future studies are needed to test more SHANK family SNPs in a large sample to demonstrate the associations.
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http://dx.doi.org/10.1002/aur.2065DOI Listing
March 2019

Association between ATM rs1801516 polymorphism and cancer susceptibility: a meta-analysis involving 12,879 cases and 18,054 controls.

BMC Cancer 2018 Nov 1;18(1):1060. Epub 2018 Nov 1.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, China.

Background: Ataxia telangiectasia mutated (ATM) gene plays a key role in response to DNA lesions and is related to the invasion and metastasis of malignancy. Epidemiological studies have indicated associations between ATM rs1801516 polymorphism and different types of cancer, but their results are inconsistent. To further evaluate the effect of ATM rs1801516 polymorphism on cancer risk, we conducted this meta-analysis.

Methods: Studies were identified according to specific inclusion criteria by searching PubMed, Web of Science, and Embase databases. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) under recessive, dominant, codominant, and overdominant models of inheritance were calculated to estimate the association between rs1801516 polymorphism and cancer risk.

Results: A total of 37 studies with 12,879 cases and 18,054 controls were included in our study. No significant association was found between rs1801516 polymorphism and cancer risk in overall comparisons (AA vs GG + GA: OR = 0.91, 95% CI, 0.78-1.07; AA+GA vs GG: OR = 1.00, 95% CI, 0.90-1.11; AA vs GG: OR = 0.89, 95% CI, 0.75-1.06; GA vs GG: OR = 1.01, 95% CI, 0.91-1.13; GG + AA vs GA: OR = 1.00, 95% CI, 0.88-1.10). However, after subgroup analyses by region-specified population, significant associations were found in European (AA vs GG + GA: OR = 0.79, 95% CI, 0.65-0.96, P = 0.017; AA vs GG: OR = 0.79, 95% CI, 0.65-0.96, P = 0.017), South American (AA+GA vs GG: OR = 2.15, 95% CI, 1.37-3.38, P = 0.001; GA vs GG: OR = 2.19, 95% CI, 1.38-3.47, P = 0.001; GG + AA vs GA: OR = 0.46, 95% CI, 0.29-0.72, P = 0.001), and Asian (AA vs GG + GA: OR = 7.45, 95% CI, 1.31-42.46, P = 0.024; AA vs GG: OR = 7.40, 95% CI, 1.30-42.19, P = 0.024). Subgroup analyses also revealed that compared with subjects carrying a GG genotype, those carrying a homozygote AA had a decreased risk for breast cancer (AA vs GG: OR = 0.76, 95% CI, 0.59-0.98, P = 0.035), and the homozygote AA was associated with decreased cancer risk in subjects with family history (AA vs GG: OR = 0.68, 95% CI, 0.47-0.98, P = 0.039).

Conclusions: ATM rs1801516 polymorphism is not associated with overall cancer risk in total population. However, for subgroup analyses, this polymorphism is especially associated with breast cancer risk; in addition, it is associated with overall cancer risk in Europeans, South Americans, Asians, and those with family history.
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http://dx.doi.org/10.1186/s12885-018-4941-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211574PMC
November 2018

Association between ApoE polymorphism and hypertension: A meta-analysis of 28 studies including 5898 cases and 7518 controls.

Gene 2018 Oct 2;675:197-207. Epub 2018 Jul 2.

The Cardiovascular Center, the First Hospital of Jilin University, Changchun 130021, China. Electronic address:

Hypertension is one of the most common chronic diseases, constituting an independent risk factor for many diseases. Our study aimed to evaluate the association between apolipoprotein E (ApoE) genetic polymorphism and hypertension, and to provide evidence for the etiology of hypertension. Case-control studies of ApoE polymorphism and hypertension, which were included in PubMed, Embase, Web of Science, Medline, WanFang, Vip, and CNKI information databases, were selected and evaluated according to criteria of inclusion and exclusion. Eligible data were extracted and pooled, and were analyzed and assessed using Stata 12.0. Random-effect models were used when heterogeneity existed in between-study, and fixed-effect models were applied otherwise. A total of 28 studies that consisted of 5898 cases with hypertension and 7518 controls were selected. Alleles and genotypes of ApoE between cases and controls were compared. For ApoE alleles, we observed the contrast of ApoE ε2 versus ε3 allele yielded a pooled OR of 0.99 (95% CI: 0.87-1.11; P = 0.823), whereas the contrast of ε4 versus ε3 allele yielded a pooled OR of 1.95 (95% CI: 1.50-2.54; P < 0.001). For ApoE genotypes, compared with ε3/ε3 genotype, genotypes (ε2/ε2 and ε2/ε3) showed a possible association with hypertension (OR = 0.88; 95% CI: 0.79-0.99; P = 0.033), and genotypes (ε3/ε4 and ε4/ε4) had a 2.08-fold risk of developing hypertension (OR = 2.08; 95% CI: 1.58-2.74; P < 0.001). There is the association between ApoE polymorphism and hypertension: the genotypes carrying ε2 allele may be a protective factor, and the ApoE ε4 allele and the genotypes carrying ε4 allele may be risk factors for hypertension.
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http://dx.doi.org/10.1016/j.gene.2018.06.097DOI Listing
October 2018

Classified status of smoking and quitting has different associations with dyslipidemia in residents in northeast China.

Clin Chim Acta 2018 Nov 8;486:209-213. Epub 2018 Aug 8.

Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun 130021, China. Electronic address:

Background: Various smoking status and high prevalence of dyslipidemia in residents exist in northeast China. However, associations of dyslipidemia with smoking status remain unclear.

Methods: A total of 17,114 participants selected by a multistage stratified cluster random sampling design were enrolled from a cross-sectional study conducted in northeast China. Associations of dyslipidemia with smoking/quitting status (smoking amount, smoking duration, and quitting duration) were investigated using multiple logistic regression.

Results: Prevalence (39.2%) of dyslipidemia existed in residents in northeast China. Smoking amount was associated with dyslipidemia (1-10 cigarettes daily: OR = 1.19, 95% CI: 1.08-1.32; 11-20 cigarettes daily: OR = 1.29, 95% CI: 1.16-1.42; and over 20 cigarettes daily: OR = 1.51, 95% CI: 1.25-1.83). Smoking duration was associated with dyslipidemia risk (6-10 years: OR = 1.75, 95% CI: 1.51-2.03; 11-15 years: OR = 1.85, 95% CI: 1.51-2.26; and ≥15 years: OR = 1.12, 95% CI: 1.02-1.23). Quitting duration (1-5 years) was associated with dyslipidemia (OR = 1.26, 95% CI: 1.07-1.48); however, we found no statistically significant associations between dyslipidemia and quitting duration (over 6 years).

Conclusions: Dyslipidemia risk is positively associated with smoking/quitting status. Smoking amount and smoking duration may co-determine dyslipidemia risk, and quitting duration (>6 years) is necessary for reducing dyslipidemia risk.
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http://dx.doi.org/10.1016/j.cca.2018.08.001DOI Listing
November 2018

Associations between three common single nucleotide polymorphisms (rs266729, rs2241766, and rs1501299) of ADIPOQ and cardiovascular disease: a meta-analysis.

Lipids Health Dis 2018 May 28;17(1):126. Epub 2018 May 28.

Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, 1163 Xinmin Street, Changchun, 130021, China.

Background: Inconsistencies have existed in research findings on the association between cardiovascular disease (CVD) and single nucleotide polymorphisms (SNPs) of ADIPOQ, triggering this up-to-date meta-analysis.

Methods: We searched for relevant studies in PubMed, EMBASE, Cochrane Library, CNKI, CBM, VIP, and WanFang databases up to 1st July 2017. We included 19,106 cases and 31,629 controls from 65 published articles in this meta-analysis. STATA 12.0 software was used for all statistical analyses.

Results: Our results showed that rs266729 polymorphism was associated with the increased risk of CVD in dominant model or in heterozygote model; rs2241766 polymorphism was associated with the increased risk of CVD in the genetic models (allelic, dominant, recessive, heterozygote, and homozygote). In subgroup analysis, significant associations were found in different subgroups with the three SNPs. Meta-regression and subgroup analysis showed that heterogeneity might be explained by other confounding factors. Sensitivity analysis revealed that the results of our meta-analysis were stable and robust. In addition, the results of trial sequential analysis showed that evidences of our results are sufficient to reach concrete conclusions.

Conclusions: In conclusion, our meta-analysis found significant increased CVD risk is associated with rs266729 and rs2241766, but not associated with rs1501299.
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http://dx.doi.org/10.1186/s12944-018-0767-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972450PMC
May 2018

Indoxyl sulfate accelerates vascular smooth muscle cell calcification via microRNA-29b dependent regulation of Wnt/β-catenin signaling.

Toxicol Lett 2018 Mar 28;284:29-36. Epub 2017 Nov 28.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China. Electronic address:

Vascular calcification (VC) is a very common phenomenon in patients with chronic kidney disease(CKD) and it increases the incidence of cardiovascular disease and leads to high mortality in CKD patients. It has been reported that some microRNAs (miRs) play roles in vascular calcification as an epigenetic regulator. Indoxyl sulfate (IS) is a protein-bound uremic toxin which has been proven as one of the major risk factors of cardiovascular disease in CKD. Here we investigated whether microRNA-29b (miR-29b) is involved in IS-induced vascular calcification. We found that vascular miR-29b was down-regulated in radial arteries of patients with end-stage renal disease. Consistently, IS also decreased miR-29b expression in human aortic smooth muscle cells (HASMCs) and potentiated their calcification. MiR-29b mimics significantly suppressed, while miR-29b anti-miR markedly enhanced, IS-induced runt-related transcription factor 2 and osteopontin expression. The expression of Wnt7b/β-catenin in radial arteries was higher in end stage renal disease than in control group, and IS increased Wnt7b/β-catenin expression in HASMCs as early as 3days after stimulation. Furthermore, miR-29b mimics potently repressed Wnt7b/β-catenin protein expression in HASMCs, whereas miR-29b anti-miR increased their expression, indicating miR-29b indeed negatively regulates Wnt7b/β-catenin signaling. Dickkopf-1 protein, the Wnt/β-catenin signaling inhibitor, suppressed anti-miR-29b-enhanced HASMCs calcification. Our data thus indicate that miR-29b downregulation and Wnt/β-catenin signaling activation may be the key mechanism of IS induced vascular calcification in chronic kidney disease.
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http://dx.doi.org/10.1016/j.toxlet.2017.11.033DOI Listing
March 2018

Hydrogen-Rich Saline Alleviates Kidney Fibrosis Following AKI and Retains Klotho Expression.

Front Pharmacol 2017 11;8:499. Epub 2017 Aug 11.

Department of Nephrology, Zhongshan Hospital, Fudan UniversityShanghai, China.

Acute kidney injury (AKI) is a prominent risk factor for the development of chronic kidney disease (CKD). To date, the related mechanism and effective therapy have not been rigorously explored. The present study aims to investigate the reno-protection of hydrogen-rich saline (HRS) against ischemia/reperfusion (IR)-induced AKI. Adult male C57 mice were randomly allocated into three groups: Sham, IR, IR+HRS. Renal IR injury model was generated via 35 min occlusion of bilateral kidney pedicles, and then, mice were administered with different treatments intraperitoneally in various groups. After 14- or 28-day treatment, mice were perfused and the kidneys were collected following reperfusion. Many proteins were detected by western blots, including renal fibrotic proteins [a-smooth muscle actin (a-SMA), collagen I (Col I)], Klotho, the methylation of Klotho, damage-regulated autophagy modulator (Beclin-1), and microtubule-associated protein light 3-II (LC3-II). Finally, the levels of serum blood urea nitrogen (BUN) and creatinine (Cr) were measured to investigate the renal function. Histological data showed that the HRS treatment significantly decreased the fibrosis in renal tissues when compared with the IR group, and both of BUN and Cr were lower in the HRS group than IR group (8.9 ± 0.6 vs. 9.9 ± 0.1 mmol/l, 51 ± 6.5 vs. 60 ± 5.8 μmol/l) ( < 0.05). The expression of fibrotic markers, a-SMA and Col I, showed a robust increase in IR injury models than the Sham group, which was consistent with the result of Trichrome staining. However, the levels of a-SMA and Col I expression were sharply decreased in the IR+HRS group ( < 0.05). IR injury also enhanced LC3-II and Beclin-1 expression, but decreased Klotho level. The Klotho level was alleviated by HRS, but LC3-II and Beclin-1 were starkly enhanced in HRS group ( < 0.05). HRS showed a protective effect in the prevention of renal injury and could inhibit renal fibrosis after IR injury in mice. This role of HRS might be exerted via retaining Klotho expression and activating autophagy in the kidney.
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http://dx.doi.org/10.3389/fphar.2017.00499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554490PMC
August 2017

Single nucleotide polymorphism rs3774261 in the AdipoQ gene is associated with the risk of coronary heart disease (CHD) in Northeast Han Chinese population: a case-control study.

Lipids Health Dis 2016 Jan 12;15. Epub 2016 Jan 12.

Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun, 130021, China.

Background: Coronary Heart Disease (CHD) is one of the leading causes of death in the world with a projected global 82 million DALYs by 2020. Genetic and environmental factors contribute to CHD development. Here, the authors investigate the association between CHD risk and three Single Nucleotide Polymorphisms (SNPs) in the AdipoQ gene (rs3774261, rs1063537 and rs2082940); and the interaction of this association with environmental factors, in Northeast Han Chinese population.

Methods: Using a case-control study design, 1514 participants (754 cases and 760 controls) were investigated. Three variants in the AdipoQ gene (rs3774261, rs1063537 and rs2082940) were selected and genotyped. The online SNPstats program and SPSS 21.0 software were used for data analyses.

Results: The authors found that the rs3774261G allele is associated with the risk of CHD but that the rs2082940T allele protects against CHD. No significant association was found between rs1063537 and CHD risk. The study also found significant interactions between triglyceride levels and the SNPs studied (P < 0.0001 for rs3774261, P = 0.014 for rs1063537, and P = 0.031 for rs2082940).

Conclusions: Variations in AdipoQ gene can protect against CHD (as with rs2082940T) or associated with CHD risk (as with rs3774261G) in Northeast Han Chinese - findings that will help shed light on the reported conflicting roles of AdipoQ in cardiovascular diseases. Serum triglycerides levels also interact in the AdipoQ - CHD association, thus further highlighting the roles environmental factors play in the genetic aspect of diseases.
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http://dx.doi.org/10.1186/s12944-015-0173-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709904PMC
January 2016

Association of Pre-miR-146a rs2910164 Polymorphism with Papillary Thyroid Cancer.

Int J Endocrinol 2015 18;2015:802562. Epub 2015 Nov 18.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China ; Jilin Provincial Key Laboratory of Molecular Epidemiology, School of Public Health, Jilin University, Changchun 130021, China.

The incidence rate of papillary thyroid cancer (PTC) has increased over the past decades, but the pathogenesis remains unclear. rs2910164, located in pre-miR-146a, has been studied in PTCs with different ethnicity, but the results were inconsistent. Here we evaluate the association between rs2910164 polymorphism and PTC and investigate the effect of this polymorphism on patients' clinicopathological characteristics. 1238 PTC patients and 1275 controls, all Han population, from Northern China, were included in our study. rs2910164 was genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Analysis of inheritance model was performed using the SNPStats program. Strength of association was assessed by odds ratio (OR) and 95% confidence interval (CI). Overall, no statistical difference in rs2910164 genotype distribution and allelic frequencies between cases and controls was found, and patients with different genotypes had similar clinicopathological characteristics in terms of stage, location, concurrent of benign thyroid tumor, and thyroiditis, while, as the number of G alleles increased, proportion of patients aged ≥45 years and those without metastasis increased (P trend < 0.001 and P trend = 0.003, resp.). However, no association remained significant after Bonferroni correction under any model of inheritance. Our results suggest no association between rs2910164 polymorphism with PTC and patients' clinicopathological characteristics.
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http://dx.doi.org/10.1155/2015/802562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667020PMC
December 2015

[Investigation on rates of awareness, treatment and control of diabetes mellitus and the influence factors in rural areas of Jilin province].

Wei Sheng Yan Jiu 2014 Sep;43(5):784-9

Objective: Assess the rates of awareness, treatment and control of diabetes mellitus and the influence factors in rural areas of Jilin province.

Methods: Multistage stratified random cluster sampling design was used to select participants that carried out with questionnaire interview and physical examination. The analysis was based on a representative sample of 923 diabetes mellitus. Multiple logistic regressions were used to examine socio-demographic factors associated with the levels of awareness, treatment and control of diabetes.

Results: Diabetes awareness, treatment, control and control among treated were 68. 9% ,57. 7% ,23. 9% and 41. 5% , respectively in rural area of Jilin province. Multivariable logistic regression analysis showed that the main effect factors on the rates of awareness were gender, family history of diabetes, smoke, drink and exercise. The rates of treatment were associated with age, occupation, family history of diabetes, drink and exercise, and the rates of control were associated gender.

Conclusions: The rates of awareness, treatment and control of diabetes mellitus were expected to be improved in rural areas of Jilin province. The effective preventive strategies which concentrate on the influence factors should be taken to control their blood glucose level.
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September 2014

[Analysis of dyslipidemia among patients with diabetes mellitus in Jilin Province communities].

Wei Sheng Yan Jiu 2014 Sep;43(5):743-8

Objective: To investigate the pattern of dyslipidemia in patients with diabetes mellitus in Jilin province communities, and to provide a theoretical basis for the management of dyslipidemia among patients with diabetes.

Method: Based on the prevalence and risk factors of chronic diseases survey among adults in Jilin Province 2012 used multistage stratified random sampling design, a total of 1825 community residents aged 18 -79 years-old with diabetes mellitus in 9 districts of Jilin Province undergo the survey with questionnaire(age, gender, history of chronic disease in the past one year), blood index detection (blood glucose, total cholesterol high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides), and anthropometric (height and weight).

Result: Among 1825 patients with diabetes, 883 males (48.4%), 942 females (51. 6%); the mean age was (55.73 + 10. 27) years old. The mean values of TG,TC,LDL-C and HDL-C were 2. 17,5.17,3.10 and 1.20 mmol/L,the mean values of TC,LDL-C and HDL-C of female were higher than male(P <0. 001). The prevalence of dyslipidenmia. was 66.9% (69.0% in, male and 65.0% in female). The prevalence of dyslipidemia in male was decreased with increasing age(P <0. 001) , the prevalence of dyslipidemia in female was increased with age (P <0. 001). In age groups of 18- , 35 - and 45 - years, the prevalence of dyslipidemia in male was higher than female (P <0. 05,P <0. 001 ,P <0. 001)', however, it was lower than female in 55 - and 65 - 79 years old grouips (P < 0.: 05). The prevalence of dyslipidemia of overweight '(71. 8%) and obesity (75. 8%) was higher than normal subjects. Among patients with diabetes, 19. 2% had high total cholesterol, 47. 8% had high triglyceride, 14. 5% had high levels of low-density lipoprotein cholesterol, 29. 2% had low high-density lipoprotein cholesterol. The proportion of diabetic patients two serum lipid values outside of clinical target were 27. 1% , the most prevalent dyslipidemia pattern among diabetic patients was a combination of TG above goal with HDL-C below target, which was observed in 17. 4 % of the patients. The second most common pattern of dyslipidemia was isolated TG increase, which was observed in 15, 9% of the patients.

Conclusion: The mean values of TG,TC, LDL-C and HDL-C among community residents with diabetes mellitus in Jilin province were higher than the general population. The prevalence of dyslipidemia in male aged 18 -54 years, female aged 55 years and above and overweight or obesity was high; the most prevalent dyslipidemia pattern among diabetic patients was a combination of TG above goal with HDL_C below target.
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September 2014

Association of ATM Gene Polymorphism with PTC Metastasis in Female Patients.

Int J Endocrinol 2014 16;2014:370825. Epub 2014 Oct 16.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China ; Jilin Provincial Key Laboratory of Molecular Epidemiology, School of Public Health, Jilin University, Changchun 130021, China.

Ataxia telangiectasia mutated (ATM) gene is critical in the process of recognizing and repairing DNA lesions and is related to invasion and metastasis of malignancy. The incidence rate of papillary thyroid cancer (PTC) has increased for several decades and is higher in females than males. In this study, we want to investigate whether ATM polymorphisms are associated with gender-specific metastasis of PTC. 358 PTC patients in Northern China, including 109 males and 249 females, were included in our study. Four ATM single nucleotide polymorphisms (SNPs) were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Association between genotypes and the gender-specific risk of metastasis was assessed by odds ratios (OR) and 95% confidence intervals (CI) under the unconditional logistic regression analysis. Significant associations were observed between rs189037 and metastasis of PTC in females under different models of inheritance (codominant model: OR = 0.15, 95% CI 0.04-0.56, P = 0.01 for GA versus GG and OR = 0.08, 95% CI 0.01-0.74, P = 0.03 for AA versus GG, resp.; dominant model: OR = 0.49, 95% CI 0.25-0.98, P = 0.04; overdominant model: OR = 0.47, 95% CI 0.25-0.89, P = 0.02). However, no association remained significant after Bonferroni correction. Our findings suggest a possible association between ATM rs189037 polymorphisms and metastasis in female PTCs.
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http://dx.doi.org/10.1155/2014/370825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216711PMC
November 2014

Association of the ATM gene polymorphisms with papillary thyroid cancer.

Endocrine 2014 Apr 8;45(3):454-61. Epub 2013 Aug 8.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, China.

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, yet few genetic markers of PTC risk useful for screening exist. Our study aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of the ataxia telangiectasia mutated (ATM) gene and PTC risk. 358 patients with PTC and 360 healthy controls were included in the case-control study. Four ATM SNPs (rs664677, rs373759, rs4988099, and rs189037) were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The analysis of genetic data was performed using the SNPStats program. The allele frequencies and genotype distributions of the four ATM SNPs were not different between PTC patients and controls. We did not observe any tendency of increasing the frequency of the risk allele from controls, patients without metastasis to patients with metastasis (P(trend) > 0.05). Interestingly, the AG genotype of rs373759 was associated with PTC risk under an overdominant model of inheritance (adjusted OR = 1.38; 95 % CI, 1.03-1.87; P = 0.03). No haplotype was observed to be significantly associated with PTC risk. Our results suggest that heterozygosity for the ATM rs373759 polymorphism may be a potential risk factor for PTC.
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http://dx.doi.org/10.1007/s12020-013-0020-1DOI Listing
April 2014