The Association Between the Peroxisome Proliferator-Activated Receptor-γ2 (PPARG2) Pro12Ala Gene Variant and Type 2 Diabetes Mellitus: A HuGE Review and Meta-Analysis

• Published in: American journal of epidemiology 2010-02, Vol.171 (6), p.645-655
• Main Authors: Gouda, Hebe N., Sagoo, Gurdeep S., Harding, Anne-Helen, Yates, Jan, Sandhu, Manjinder S., Higgins, Julian P. T.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; diabetes mellitus; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; epidemiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; genetics; genome; human; HUMAN GENOME EPIDEMIOLOGY (HuGE) REVIEW; Medical sciences; meta-analysis; PPAR gamma; review; type 2
• ISSN: 0002-9262; 1476-6256
• DOI: 10.1093/aje/kwp450

The peroxisome proliferator-activated receptor-γ gene (PPARG) has been implicated in the etiology of type 2 diabetes mellitus and has been investigated in numerous epidemiologic studies. In this Human Genome Epidemiology review, the authors assessed this relation in an updated meta-analysis of 60 association studies. Electronic literature searches were conducted on September 14, 2009. Population-based cohort, case-control, cross-sectional, or genome-wide association studies reporting associations between the PPARG Pro12Ala gene variant (rs1801282) and type 2 diabetes were included. An updated literature-based meta-analysis involving 32,849 type 2 diabetes cases and 47,456 controls in relation to the PPARG Pro12Ala variant was conducted. The combined overall odds ratio, calculated by per-allele genetic model random-effects meta-analysis for type 2 diabetes and the Pro12Ala polymorphism, was 0.86 (95% confidence interval: 0.81, 0.90). The analysis indicated a moderate level of heterogeneity attributable to genuine variation in gene effect size (I2 = 37%). This may reflect the variation observed between ethnic populations and/or differences in body mass index. Work on PPARG Pro12Ala should now focus on the observed heterogeneity in the magnitude of the association between populations. Further investigations into gene-gene and gene-environment interactions may prove enlightening.