Association of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) gene polymorphisms and type 2 diabetes mellitus: a meta-analysis

Background The association between peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) polymorphisms and type 2 diabetes mellitus (T2DM) has been investigated in several studies, but these studies yielded contradictory results. We conducted a meta-analysis to assess the association between three polymorphisms (Gly482Ser, Thr394Thr and Thr612Met) in PPARGC1A and T2DM. Methods A literature-based search was conducted to collect data. The additive model was chosen to investigate the association between the three polymorphisms and T2DM. The random effects model was used if there was heterogeneity between studies. In addition, subgroup meta-analyses were made according to the ethnic groups. Results Twenty-three studies were enrolled in this meta-analysis (7539 cases and 9562 controls for Gly482Ser, 1818 cases and 2376 controls for Thr394Thr, 2042 cases and 1289 controls for Thr612Met). In the combined analysis of all eligible studies, a significant association was found between Gly482Ser, Thr394Thr and T2DM with pooled odds ratios 1.19 [95% confidence interval (CI) 1.05-1.34] and 1.33 (95% CI 1.04-1.70), respectively, but great heterogeneity was found between studies. In the subgroup meta-analyses, we found that Gly482Ser and Thr394Thr polymorphisms were associated with the risk of T2DM, and the pooled odds ratios were 1.66 (95% CI 1.28-2.15) and 1.72 (95% CI 1.45-2.03), respectively, in the Indian population; no significant evidence was found in the Caucasian and East Asian populations. Conclusions This meta-analysis indicated that Gly482Ser and Thr394Thr polymorphisms of PPARGC1A gene were significantly associated with the risk of T2DM, especially in the Indian population. No relationship was found between the Thr612Met and risk of T2DM. Copyright (C) 2011 John Wiley & Sons, Ltd.