Gly482Ser polymorphism in the peroxisome proliferator–activated receptor γ coactivator–1α gene is associated with oxidative stress and abdominal obesity

Abstract 

The objective of the study was to o investigate the relationship of the Gly482Ser (G482S) polymorphism in the peroxisome proliferator–activated receptor γ coactivator–1α (PPARGC1A) gene and type 2 diabetes mellitus (T2DM), obesity, and oxidative status in Chinese adults. We enrolled 276 T2DM patients and 1049 nondiabetic subjects aged at least 35 years. The G482S variant was detected using polymerase chain reaction and restriction enzyme digestion. The levels of thiobarbituric acid reactive substance, an indicator of lipid peroxidation, were measured in plasma samples. The homeostasis model assessment–estimated insulin resistance (HOMA-IR) index was determined for nondiabetic subjects. P values were adjusted for age, sex, and body mass index by using a generalized linear model. In this series, there was no association between G482S polymorphism and T2DM and obesity (body mass index >25 kg/m²). However, the plasma fasting insulin levels and HOMA-IR indices were significantly higher in nondiabetic subjects harboring the variant (S/S) genotype than in those with the heterozygous (G/S) genotype. With regard to the effect of the different genotypes on body fat distribution, overweight nondiabetic subjects harboring the S/S or G/S genotype had a significantly higher waist-to-hip ratio than those with the wild-type (G/G) genotype. Furthermore, subjects with the S/S genotype had significantly higher serum thiobarbituric acid reactive substance levels than those with the G/G genotype; the diabetic group mainly contributed to this significant association (P < .001). In overweight, nondiabetic Chinese adults, G482S polymorphism in the PPARGC1A gene is associated with hyperinsulinemia, HOMA-IR indices, and abdominal obesity. Furthermore, in hyperglycemia, the S482 allele is related to increased oxidative stress.