Association between PGC-1alpha gene polymorphisms and type 2 diabetes risk: a case-control study of an Iranian population

Objective: The peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) gene could play a role in the onset of type 2 diabetes mellitus. The aim of this study was to explore the possible associations among polymorphisms Gly482Ser, Thr394Thr and Thr528Thr of the PGC-1alpha gene and the risk of type 2 diabetes in Kurdish-Iranians.

Methods: DNA specimens from all 173 type 2 diabetes subjects and 173 normoglycemic subjects were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Genotypic and allelic frequencies were analyzed in each group. Serum lipids, fasting glucose, fasting serum insulin, homeostasis model assessment of insulin resistance and glycated hemoglobin levels were determined using the conventional methods. The data were analyzed using SPSS software.

Results: The GA genotype of Gly482Ser was associated with a significant susceptibility for type 2 diabetes (odds ratio 5.23, p<0.000). Furthermore, the GA genotype of Thr528Thr had a higher risk for type 2 diabetes (odds ratio 2.37, p<0.002). Normoglycemic persons carrying the GA+AA genotypes of Gly482Ser variation had significantly lower high-density lipoprotein cholesterol in comparison with persons having GG genotype. In comparison with GG genotype carriers, normoglycemic subjects carrying the GA+AA genotypes of Thr394Thr variation had significantly higher fasting blood sugar, fasting serum insulin and homeostasis model assessment of insulin resistance. Normoglycemic subjects with the GA+AA genotypes of Thr528Thr variation had significantly higher levels of low-density lipoprotein cholesterol compared with subjects having the GG genotype. Type 2 diabetes subjects carrying the GA+AA genotypes of this polymorphism had significantly higher waist-hip ratio in comparison with the GG genotype carriers. We also found that haplotype 394-GG/482-GA/528-GG of PGC-1alpha was significantly associated with higher risk of type 2 diabetes.

Conclusions: Our findings revealed significant associations between PGC-1alpha Gly482Ser and Thr528Thr polymorphisms and type 2 diabetes in Kurdish-Iranians.