The Ala allele in the PPAR-γ2 gene is associated with reduced risk of type 2 diabetes mellitus in Caucasians and improved insulin sensitivity in overweight subjects

The purpose of the present study was to identify the association of the Pro12Ala polymorphism in the PPAR-gamma 2 gene with diabetes, insulinaemia and insulin resistance. A meta-analysis study was carried out based on studies conducted in the last 10 years, using the databases PubMed, ISI Web of Knowledge, High Wire Press and Scielo, and the reference lists of the obtained articles. We included original studies that showed the relationship between the Pro12Ala polymorphism in the PPAR-gamma 2 gene and type 2 diabetes mellitus (T2DM), insulinaemia and insulin resistance. Statistical analyses were conducted using the program RevMAn 5.0. The Mantel-Haenszel test was used to estimate the OR and the 95% CI of the dichotomous variable, while the standardised effect size was used to estimate the average standardised mean difference and 95% CI of continuous variables. The studies were subgrouped by ethnicity and overweight status. Forty-one studies were analysed, including a global sample of 30 612 subjects. We found a significant association of the Ala allele with the lowest risk of T2DM in Caucasians (OR 0.80; 95% CI 0.65, 0.98), lower serum insulin (standardised effect size: -0.05; 95% CI -0.09, -0.00; P = 0.04), and greater sensitivity to insulin in overweight individuals (homeostasis model assessment of insulin resistance standardised effect size: -0.07; 95% CI -0.13, -0.01; P = 0.02). Considering that the Pro12Ala polymorphism in the PPAR-gamma 2 gene is one of the factors related to insulin sensitivity, the present study demonstrated a significant effect of the Ala allele on lower development of T2DM in Caucasians and greater sensitivity to insulin in overweight subjects.