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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.,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.


Luo W.,U.S. Center 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.,U.S. Center 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 | 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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