Abstract
The peroxisome proliferator-activated receptor-gamma (IPIPAR gamma) is a nuclear receptor involved in lipid metabolism, adipocyte differentiation and regulation of insulin sensitivity, and is associated with Type 2 diabetes (T2DM). The association of the C1431T silent mutation and the Pro 12Ala missense transversion within the PPAR gamma gene with the development of T2DM or obesity has often yielded contradictory results. We examined the association of the PPAR gamma Pro 12Ala and C1431 T gene variants and their haplotypes with the susceptibility to T2DM. This was a retrospective study involving 491 T2DM patients and 400 age- and gender-matched controls. Pro12Ala and C1431T genotyping was done by PCR-RFLP analysis. Comparable frequencies of the mutant 12Ala (0.07 vs 0.08, p=0.216) and 1431T (0.12 vs; 0.10, p=0.189) alleles, and Pro12Ala (p=0.218) and C1431T(p=0.421) genotypes were seen between patients and in nondiabetic control subjects. While no difference was noted in the distribution of Pro12AlaC1 431T haplotypes and genotypes between patients and controls, the PPAR gamma 12Ala, but not 1431T, allele was significantly associated with lower body mass index (BMI) (<= 25.0) among patients. Regression analysis confirmed the association of the Pro12Ala (odds ratio =5.340; 95% confidence interval =1.044-27.311) with normal (BMI<25.0) but not with overweight/obesity among T2DM patients. Despite its association with lower BMI among T2DM patients, the PPAR gamma gene does not appear to markedly influence Type 2 diabetes among Tunisian subjects.