Association of Peroxisome Proliferator-Activated Receptor ^|^alpha;/^|^delta;/^|^gamma; With Obesity, and Gene^|^ndash;Gene Interaction, in the Chinese Han Population

Wenshu Luo,Chao Hao,Zhengyuan Zhou,Xiaoshu Hu,Zhirong Guo,Xingjuan Yao,Ming Wu,Jingchao Liu,Lijun Zhang,Zhiwu Zhou

doi:10.2188/jea.je20120110

Abstract

BackgroundWe 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.MethodsParticipants 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.ResultsAfter covariate adjustment, minor alleles of rs2016520 in PPARδ and rs10865170 in PPARγ 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.Conclusionsrs2016520 and rs10865170 were associated with lower obesity risk. In addition, interaction was identified among rs2016520, rs9794, and rs10865170 in obesity.

Highlights

Obesity is a complex metabolic disorder that affects a growing number of people worldwide[1] and is the result of both genetic and environmental factors
Whereas peroxisome proliferator-activated receptor α (PPARα) and PPARγ are predominant in liver and adipose tissue, respectively, PPARα is involved in fat metabolism and fatty acid oxidation whereas PPARγ influences adipocyte differentiation and insulin action
Odds ratios showed an association of genotypes of variants in rs2016520 and rs10865710 with decreased obesity risk, after adjustment for all confounders: obesity risk was significantly higher in individuals with

Summary

Introduction

Obesity is a complex metabolic disorder that affects a growing number of people worldwide[1] and is the result of both genetic and environmental factors. PPARδ is abundantly expressed throughout the body but at low levels in liver; its function is not yet fully understood. Consistent with their expression profiles, the PPARs have. 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. Interaction was identified among rs2016520, rs9794, and rs10865170 in obesity

Methods

Results

Conclusion