Effect of polymorphisms in the PPARGC1A gene on body fat in Asian Indians

Abstract

Objective: To evaluate whether polymorphisms in the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PPARGC1A) gene were related to body fat in Asian Indians. Methods: Three polymorphisms of PPARGC1A gene, the Thr394Thr, Gly482Ser and +A2962G, were genotyped on 82 type 2 diabetic and 82 normal glucose tolerant (NGT) subjects randomly chosen from the Chennai Urban Rural Epidemiology Study using PCR-RFLP, and the nature of the variants were confirmed using direct sequencing. Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies using an expectation-maximization algorithm. Visceral, subcutaneous and total abdominal fat were measured using computed tomography, whereas dual X-ray absorptiometry was used to measure central abdominal and total body fat. Results: None of the three polymorphisms studied were in LD. The genotype (0.59 vs 0.32, P=0.001) and allele (0.30 vs 0.17, P=0.007) frequencies of Thr394Thr polymorphism were significantly higher in type 2 diabetic subjects compared to those in NGT subjects. The odds ratio for diabetes (adjusted for age, sex and body mass index) for the susceptible genotype, XA (GA+AA) of Thr394Thr polymorphism, was 2.53 (95% confidence intervals: 1.30-5.04, P=0.009). Visceral and subcutaneous fat were significantly higher in NGT subjects with XA genotype of the Thr394Thr polymorphism compared to those with GG genotype (visceral fat: XA 148.2plusminus46.9 vs GG 106.5plusminus51.9 cm², P=0.001; subcutaneous fat: XA 271.8plusminus167.1 vs GG 181.5plusminus78.5 cm², P=0.001). Abdominal (XA 4521.9plusminus1749.6 vs GG 3445.2plusminus1443.4 g, P=0.004), central abdominal (XA 1689.0plusminus524.0 vs GG 1228.5plusminus438.7 g, P<0.0001) and non-abdominal fat (XA 18763.8plusminus8789.4 vs GG 13160.4plusminus4255.3 g, P<0.0001) were also significantly higher in the NGT subjects with XA genotype compared to those with GG genotype. The Gly482Ser and +A2962G polymorphisms were not associated with any of the body fat measures. Conclusion: Among Asian Indians, the Thr394Thr (G right arrow A) polymorphism is associated with increased total, visceral and subcutaneous body fat.