Interaction between Calpain-5, Peroxisome proliferator-activated receptor-gamma and Peroxisome proliferator-activated receptor-delta genes: a polygenic approach to obesity.

Maria E Saez,Antonio Gonzalez-Perez,Maria T Martinez-Larrad,Manuel Serrano-Rios,Antonio Grilo,Francisco J Moron,Reposo Ramirez-Lorca,Agustin Ruiz,Francisco J Serrano-Hernando,Luis Manzano

doi:10.1186/1475-2840-7-23

Abstract

ContextObesity is a multifactorial disorder, that is, a disease determined by the combined effect of genes and environment. In this context, polygenic approaches are needed.ObjectiveTo investigate the possibility of the existence of a crosstalk between the CALPAIN 10 homologue CALPAIN 5 and nuclear receptors of the peroxisome proliferator-activated receptors family.DesignCross-sectional, genetic association study and gene-gene interaction analysis.SubjectsThe study sample comprise 1953 individuals, 725 obese (defined as body mass index ≥ 30) and 1228 non obese subjects.ResultsIn the monogenic analysis, only the peroxisome proliferator-activated receptor delta (PPARD) gene was associated with obesity (OR = 1.43 [1.04–1.97], p = 0.027). In addition, we have found a significant interaction between CAPN5 and PPARD genes (p = 0.038) that reduces the risk for obesity in a 55%.ConclusionOur results suggest that CAPN5 and PPARD gene products may also interact in vivo.

Highlights

Obesity, which is among of the most hereditable human conditions (45–75%), is, with few exceptions, a polygenic disorder determined by an unknown number of genes with mild to moderate individual effects that interacts with the environment to produce the phenotype
In the monogenic analysis, only the peroxisome proliferator-activated receptor delta (PPARD) gene was associated with obesity (OR = 1.43 [1.04–1.97], p = 0.027)
We have found a significant interaction between calpain 5 (CAPN5) and PPARD genes (p = 0.038) that reduces the risk for obesity in a 55%

Summary

Introduction

Obesity, which is among of the most hereditable human conditions (45–75%), is, with few exceptions, a polygenic disorder determined by an unknown number of genes with mild to moderate individual effects that interacts with the environment to produce the phenotype. Association analysis has been the more successful strategy for the identification of these genetic factors, but these studies are not always replicated in subsequent analyses and only a small proportion of these genes have been consistently associated with the disease [2]. Genetic studies have greatly contributed to corroborate the role of PPARG in the pathogenesis of metabolic syndrome related phenotypes: the Pro12Ala polymorphism of PPARG gene has been confirmed to be associated with greater body mass index (BMI) and insulin sensitivity in the obese subgroup in a recent meta-analysis with more than 32.000 individuals[10]

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Conclusion