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Zhu Q.,Soochow University of China | Zhu Q.,Center for Disease Control of XiuZhou | Guo Z.,Soochow University of China | Hu X.,Health Bureau of JiangSu Province | And 4 more authors.
Herz | Year: 2014

Background: There is strong evidence suggesting an association between the peroxisome-activated receptor γ (PPARγ) gene and multimetabolic disorders. The association of PPARγ genetic variants with essential hypertension (EH) has not yet been investigated. The aim of this study was to investigate the association between the PPARγ gene (C681G and intron CT) and EH, examining the polymorphism and haplotype in a Han Chinese population. Methods: Participants were recruited within the framework of the PMMJS cohort population survey in an urban community of Jiangsu Province, China. Two single-nucleotide polymorphisms (SNPs) previously reported to be associated with multimetabolic disorders and the reasonable coverage of the PPARγ gene region were analyzed with TaqMan SNP genotyping assays. Results: C681G and intron CT were significantly associated with an increased risk of EH both in the codominant model and the dominant model after adjusting for potential nongenetic risk factors. Analysis of the haplotype association revealed that the risk of EH was significantly increased among individuals carrying the GC (odds ratio, 95∈% CI: 1.60, 1.21-2.11), CT (1.45, 1.03-2.11), and GT haplotypes (1.95, 1.17-3.23) compared with those carrying the CC haplotype. Conclusion: The polymorphisms of C681G and intron CT were significantly associated with the risk of EH, and the GC, CT, and GT haplotypes established by C681G and intron CT are likely to be genetic markers of EH in the Han Chinese population. © 2013 Urban & Vogel.


Luo W.,Centers for Disease Control and Prevention | Luo W.,Soochow University of China | Guo Z.,Soochow University of China | Wu M.,Center for Disease Control of Jiangsu Province | And 7 more authors.
Journal of Epidemiology | Year: 2013

Background: We investigated the association of 10 single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (PPARs) with obesity and the additional role of gene-gene interaction. Methods: Participants were recruited within the framework of the Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province cohort population survey of an urban community in China. In total, 820 subjects (513 nonobese adults, 307 obese adults) were randomly selected, and no individuals were consanguineous.Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806, and rs4684847) were genotyped and analyzed. Results: After covariate adjustment, minor alleles of rs2016520 in PPARd and rs10865170 in PPAR? were associated with lower BMI (P < 0.01 for all). Generalized multifactor dimensionality reduction analysis showed significant gene-gene interaction among rs2016520, rs9794, and rs10865170 in 3-dimensional models (P = 0.0010); prediction accuracy was 0.6011 and cross-validation consistency was 9/10. It also showed significant gene-gene interaction between rs2016520 and rs10865170 in all 2-dimensional models (P = 0.0010); prediction accuracy was 0.6072 and cross-validation consistency was 9/10. Conclusions: rs2016520 and rs10865170 were associated with lower obesity risk. In addition, interaction was identified among rs2016520, rs9794, and rs10865170 in obesity. © 2013 Japan Epidemiological Association.


Luo W.,Centers for Disease Control and Prevention | Luo W.,Soochow University of China | Guo Z.,Soochow University of China | Wu M.,Center for Disease Control of Jiangsu Province | And 3 more authors.
Journal of Cardiovascular Medicine | Year: 2014

OBJECTIVE: To compare the suitability of metabolic syndrome definitions in predicting cardiovascular disease (CVD) risk. METHODS: We analyzed data from a population-based prospective cohort of 3598 participants from Jiangsu, China. Waist circumference was replaced with central obesity [index of central obesity (ICO), a ratio of waist circumference and height] in Cholesterol Education Program Adult Treatment Panel III (ICO-replaced ATPIII) and International Diabetes Federation (ICO-replaced IDF), respectively. Cox proportional-hazards regression model and the receiver operating characteristic curve (ROC curve) was used to evaluate the suitability of ATPIII, IDF, ICO-replaced IDF and ICO-replaced ATPIII in predicting CVD risk. RESULTS: ICO was a better parameter in predicting CVD risk by ROC curve analysis. The ROC curve analysis also showed that although ICO-replaced IDF and IDF had the higher degree of specificity, lower sensitivity, longer ROC curve distance, less area under the curve to identify CVD than ATPIII and ICO-replaced ATPIII, therefore ICO-replaced IDF and IDF seemed to be undesirable. However, there was no significant difference in area under the curve between ATPIII and ICO-replaced ATPIII in predicting CVD risk. But it seems that odds ratios for abnormal triglyceride and high-density lipoprotein levels increase slightly when using ICO, but decrease for hyperglycemia and hypertension when using ICO. CONCLUSION: ICO was a better predictor of abnormal triglyceride and high-density lipoprotein levels than waist circumference, but waist circumference was a better predictor of hyperglycemia and hypertension than ICO. However, we failed to support ICO as a better parameter for metabolic syndrome definition in predicting CVD risk compared with waist circumference. © 2014 Italian Federation of Cardiology.


Gu S.-J.,Soochow University of China | Liu M.-M.,Soochow University of China | Guo Z.-R.,Soochow University of China | Wu M.,Center for Disease Control of Jiangsu Province | And 4 more authors.
Gene | Year: 2013

The peroxisome proliferator-activated receptors (PPARs)-α,-β/δ and -γ are the ligand-activated transcription factors that function as the master regulators of glucose, fatty acid and lipoprotein metabolism, energy balance, cell proliferation and differentiation, inflammation and atherosclerosis. This study examined the main effects of both single-locus and multilocus interactions among genetic variants in Chinese Han individuals to test the hypothesis that PPAR-α/δ/γ polymorphisms may contribute to the etiology of hypertriglyceridemia independently and/or through such complex interactions. We genotyped 9 single nucleotide polymorphisms for PPAR-α/δ/γ. Participants were recruited from the Prevention of MetS and Multi-metabolic Disorders in Jiangsu Province of China Study. 820 subjects (474 non-hypertriglyceridemia subjects, 346 hypertriglyceridemia subjects) were randomly selected. Single-locus analyses showed that after adjusted for age, sex, smoking, alcohol consumption, body mass index, waist circumference and fasting glucose, rs1800206, rs9794, rs3856806 and rs1805192 were significantly associated with hypertriglyceridemia, the OR (95% CI) were 4.43(3.08-6.37), 1.49(1.10-2.02), 1.56(1.16-2.08), 2.43(1.80-3.29), respectively. Further, generalized multifactor dimensionality reduction method analysis showed that two-to-six-locus and eight-locus models were significant (p. <. 0.05), which indicated a potential gene-gene interaction among PPAR-α/δ/γ polymorphisms. The results suggest that PPAR-α/δ/γ polymorphisms may contribute to the risk of hypertriglyceridemia independently and/or in an interactive manner. © 2012 Elsevier B.V.


Fan W.,Soochow University of China | Shen C.,Soochow University of China | Wu M.,Center for Disease Control of Jiangsu Province | Zhou Z.-Y.,Center for Disease Control of Changshu | Guo Z.-R.,Soochow University of China
Genetic Testing and Molecular Biomarkers | Year: 2015

Aims: Elevated low-density lipoprotein-cholesterol (LDL-C) is regarded as one of major risks of cardiovascular diseases and atherosclerotic events. It has been previously reported that peroxisome proliferator-activated receptors (PPARs) play an important role in the regulation of lipid metabolism. In this study, we aimed to investigate the influence of PPARα/δ/γ gene polymorphisms on LDL-C level. Eight hundred twenty unrelated participants were recruited. Ten single-nucleotide polymorphisms (SNPs) were genotyped to analyze the gene-gene interactions among these polymorphisms using the generalized multifactor dimensionality reduction (GMDR) method. Results: The results of single-locus analyses indicated that the genotypes with minor allele variants at the rs1800206, rs9794, rs1805192, rs709158, and rs3856806 loci are associated with higher LDL-C levels (p<0.05) after adjusting for covariates. In contrast, individuals that were homozygous for the major allele (CC) of rs10865710 had significantly higher LDL-C than those with either one or more minor type alleles (CG+GG, mean difference: -0.21 mM; 95% confidence interval [CI]: -0.37 to -0.04 mM; p=0.013). Significant gene-gene interactions among PPAR gene polymorphisms on LDL-C were identified by a generalized multifactor dimensionality reduction (GMDR) approach in 2- to 8-locus models (p<0.05). Conclusion: Our results provide evidence that multiple PPARα/δ/γ gene polymorphisms are individually associated with increased LDL-C, and that interactions, among these alleles result in additional increased risk suggesting that PPAR genes may contribute substantially to the risk of cardiovascular diseases and atherosclerosis. © Copyright 2015, Mary Ann Liebert, Inc.


Gu S.-J.,Center for Disease Control of Changshu | Gu S.-J.,Soochow University of China | Chen D.-H.,The Center for Disease Control and Prevention of Suzhou Industry Park | Guo Z.-R.,Soochow University of China | And 3 more authors.
Endocrine | Year: 2014

The peroxisome proliferator-activated receptors (PPARs)-α, -β/δ, and -γ are the ligand-activated transcription factors that function as the master regulators of glucose, fatty acid and lipoprotein metabolism, inflammation, and atherosclerosis. Our aim was to test the association between ten single nucleotide polymorphisms of PPARs and CRP level, as well as their interaction with overweight/obesity. A sample population of 643 subjects was recruited from the prevention of MetS and multi-metabolic disorders in Jiangsu Province of China Study. The selected SNPs in PPAR α (rs135539, rs4253778, rs1800206), PPAR β/δ (rs2016520 and rs9794), and PPAR γ (rs10865710, rs1805192, rs709158, rs3856806, and rs4684847) were genotyped. After adjustment for smoking, alcohol consumption, SBP, DBP, TG, and HDL-C, rs1800206, rs709158, rs1805192, and rs4684847 polymorphisms were significantly associated with CRP level in normal weight subjects (P < 0.05). In the overweight/obese subjects, rs1800206 was also significant associated with CRP level (P < 0.01). In addition, the rs709158, rs1805192, and rs4684847 polymorphisms were shown interactions with overweight/obesity to influence CRP level (P < 0.05). PPARs polymorphisms are independently associated with CRP levels in Chinese Han population. Further, PPARs polymorphisms interact with overweight/obesity to set CRP levels. © 2014 Springer Science+Business Media New York.


Luo W.,Soochow University of China | Luo W.,Center for Disease Control of ChangZhou | Guo Z.,Soochow University of China | Hu X.,Health Bureau of JiangSu Province | And 4 more authors.
International Journal of Cardiology | Year: 2013

Background: Few prospective studies on association between waist circumference and hypertension have taken account of the dynamic change of WC, which caused by lifestyle modification. Methods: After a baseline investigation, we conducted the first and the second follow-up assessments for subjects after 2 and 5 years, respectively. The difference value (D-value, the value at the first follow-up minus the value at baseline) in WC was calculated to evaluate 2 years change of WC. The association between 2 years change of WC and incident hypertension was analyzed by using Cox proportional hazards regression model. Results: Among 2778 participants free of hypertension at baseline and the first follow-up, 660 (23.8%) subjects developed hypertension over a period of 5 years (between the first and the second follow-up assessments). In both genders, the incidence density and HRs of hypertension were all increased with WC D-value regardless of their abdominal obesity status at baseline. Compared with participants who were non-abdominal obese both at baseline and first follow up, hypertension risk was higher in subjects who were abdominal obese both at baseline and the first follow-up, and in subjects who were non-abdominal obese at baseline but with abdominal obesity at the first follow up. Conclusions: WC dynamic change was associated with incident hypertension, and more WC reduction was associated with more hypertension risk decrease. © 2012 Elsevier Ireland Ltd.


Gu S.-J.,Center for Disease Control of Changshu | Gu S.-J.,Soochow University of China | Guo Z.-R.,Soochow University of China | Zhou Z.-Y.,Center for Disease Control of Changshu | And 2 more authors.
Lipids in Health and Disease | Year: 2014

Background: The PPAR and PPAR γ are the key messengers responsible for the translation of nutritional stimuli into changes for the expression of genes, particularly genes involved in lipid metabolism. However, the associations between PPAR / γ polymorphisms and lipid serum levels in the general population were rarely studied, and the conclusions were conflicting. The objective was to investigate the associations of the PPAR and PPAR γ polymorphisms with dyslipidemia. Methods. 820 subjects were randomly selected from the Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province cohort populations. The logistic regression model was used to examine the association between these polymorphisms and dyslipidemia. SNPstats was used to explore the haplotype association analyses. Results: In the codominant and log-additive models, rs1800206, rs1805192 and rs3856806 were all associated with dyslipidemia (P < 0.005). When the most common haplotype L-G (established by rs1800206, rs4253778) was treated as the reference group, the V-G haplotype was associated with dyslipidemia (P < 0.001), higher TC and TG levels (P < 0.01). Moreover, when compared to Pro-C haplotype (established by rs1805192, rs3856806), the Pro-T, Ala-C, Ala-T haplotypes were associated with dyslipidemia (p < 0.001). A-T haplotype was associated with higher TC levels, (p < 0.01), and the P-T, A-C, A-T haplotypes were associated with higher TG levels (p < 0.01). Conclusions: PPAR and PPAR γ polymorphisms and haplotypes may be the genetic risk factors for dyslipidemia. © 2014 Gu et al.;licensee BioMed Central Ltd.


Gu S.-J.,Center for Disease Control of Changshu | Gu S.-J.,Soochow University of China | Guo Z.-R.,Soochow University of China | Zhou Z.-Y.,Center for Disease Control of Changshu | And 3 more authors.
Molecular Medicine Reports | Year: 2014

Peroxisome proliferator-activated receptor γ (PPARγ) may play an important role in lipid metabolism directly or by inducing the transcription of target genes. The aim of the present study was to investigate the association between common variants at the PPARγ locus (C1431T and Pro12Ala polymorphisms) and lipid serum levels. The studied population consisted of 820 subjects randomly selected from the Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province cohort population. All subjects were interviewed and blood samples were obtained for laboratory analysis and DNA extraction. The TaqMan single nucleotide polymorphism genotyping assay was used for polymorphism genotyping. Individual polymorphisms and haplotype data were available for analysis. The 12Ala allele was found to be associated with significantly increased levels of triglyceride (TG) (P<0.01), whilst the 1431T allele was found to be associated with significantly increased levels of TG, total cholesterol (TC) and non-high-density lipoprotein (non-HDL) (P<0.01). When P-C, the most common haplotype, was used as the reference group, the P-T, A-C and A-T haplotypes were found to be associated with significantly increased levels of TG (P<0.01). In addition, the A-T haplotype was shown to be associated with significantly increased levels of TC and non-HDL (P<0.01). In conclusion these results suggest that PPARγ gene variability may increase the risk of dyslipidemia.


Gu S.-J.,Soochow University of China | Guo Z.-R.,Soochow University of China | Wu M.,Center for Disease Control of Jiangsu Province | Ding Y.,Soochow University of China | Luo W.-S.,Soochow University of China
Genetic Testing and Molecular Biomarkers | Year: 2013

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor involved in the regulation of several biochemical pathways. Blood pressure-lowering effects have been found in PPARγ agonists in several hypertensive models. The biology and research data related to the gene suggest that it could play a role in essential hypertension (EH) susceptibility. This study aimed to investigate the association between PPARγ polymorphisms and EH. About 820 subjects were genotyped for the three single-nucleotide polymorphisms used as genetic markers for the PPARγ genes (C681G, Prol2Ala, and C1431T). After correction for age, sex, smoking, alcohol consumption, body mass index, waist circumference, and fasting glucose, the G allele (CG+GG) of C681G was significantly associated with the increase in the risk of EH (odds ratio [OR]=1.54, 95%confidence interval [CI]: 1.14-2.09, p=0.005). The A allele (PA+PP) of Pro12Ala was significantly associated with the decrease in the risk of EH (OR=0.70, 95%CI: 0.52-0.95, p=0.020). However, C1431T was not significantly associated with EH. Generalized multifactor dimensionality reduction analysis showed that there was a potential gene-gene interaction between C681G and Prol2Ala (p=0.0107). The G-P haplotype (established by C681G, Prol2Ala) was significantly associated with increase in the risk of EH (OR=1.53, 95%CI:1.13-2.07, p=0.006). In conclusion, PPARγ polymorphisms and haplotypes were significantly associated with hypertension susceptibility. © Copyright 2013, Mary Ann Liebert, Inc.

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