Pro12Ala variant of the PPARG2 gene increases body mass index: An updated meta-analysis encompassing 49,092 subjects

Abstract

Objective The peroxisome proliferator-activated receptor gamma 2 (PPARG2) gene has been intensively studied with relation to obesity and metabolic disorders. Indeed, a large number of studies assessing the association between the PPARG2 polymorphism Pro12Ala (rs1801282) and body mass index (BMI) have been published with some controversial results. In this meta-analysis, the effects of Pro12Ala polymorphism of the PPARG2 gene on BMI were investigated.

Design and Methods Externally published data were collected and we included our own novel data from a study in the elderly participants (>55 years) of a Mediterranean cohort, the SUN (“Seguimiento Universidad de Navarra”) Project (n = 972). A total of 75 independent studies with 49,092 subjects (39,806 with the genotype Pro12Pro and 9,286 carrier subjects of the Ala allele) were included.

Results The meta-analysis revealed a higher BMI with an overall estimation of +0.065 kg/m2 (95%CI = 0.026-0.103, P = 0.001) for homo-/heterozygous carriers of the Ala allele of the PPARG2 gene in comparison to non-carriers. The analysis also showed that there was heterogeneity (P for heterogeneity <0.001), but funnel plots did not suggest apparent publication bias. Furthermore, the association between the Pro12Ala polymorphism of the PPARG2 gene and increased BMI was stronger in Caucasian. Thus, carriers of the Ala allele had significantly higher BMI than non-carriers in a subsample of 6,528 Caucasian male subjects (standardized mean difference = 0.090, 95%CI=0.032-0.148, P = 0.002, P for heterogeneity = 0.121).

Conclusion This updated meta-analysis showed that carriers of the Ala12 allele of the PPARG2 gene had a higher average BMI.