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

• Published in: International Journal of Obesity Vol. 30; no. 6; pp. 884 - 891
• Main Authors: Vimaleswaran, K S, Radha, V, Anjana, M, Deepa, R, Ghosh, S, Majumder, P P, Rao, M R S, Mohan, V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2006; Nature Publishing; Nature Publishing Group
• Subjects: Abdomen; abdominal fat; Absorptiometry, Photon; adipose tissue; Adipose Tissue - pathology; Adult; Algorithms; Anthropometry; Anthropometry - methods; Asian Continental Ancestry Group - genetics; Asian People; Asians; Biological and medical sciences; Body Composition; Body Composition - genetics; Body fat; Body mass index; Case-Control Studies; Computed tomography; Diabetes; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; dual-energy X-ray absorptiometry; Epidemiology; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; General aspects; Genes; genetic polymorphism; genetics; Genotype; Genotype & phenotype; Glucose; Glucose Tolerance Test; Health Promotion and Disease Prevention; Heat-Shock Proteins; Heat-Shock Proteins - genetics; human diseases; human genetics; human physiology; Humans; India; Internal Medicine; Intra-Abdominal Fat; Intra-Abdominal Fat - pathology; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; methods; Middle Aged; noninsulin-dependent diabetes mellitus; Obesity; original-article; pathology; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; peroxisomes; Polymerase Chain Reaction; Polymerase Chain Reaction - methods; Polymorphism; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Public Health; subcutaneous fat; Subcutaneous Fat - pathology; Tomography; Tomography, X-Ray Computed; Transcription Factors; Transcription Factors - genetics; transcriptional activation; Vertebrates: anatomy and physiology, studies on body, several organs or systems; visceral fat; Canada; Quebec Canada; India; computed tomography; genetics; total body fat; dual X-ray absorptiometry; Asian Indians; Obesity; Asiatic; Radiodiagnosis; Nutrition; Nutrition disorder; Metabolic diseases; Fat mass; Ethnic group; Osteoarticular system; X ray absorption spectrometry; Gene; Medical imagery; Genetics; Indian; Densitometry; Bone; Nutritional status; Polymorphism; PPARCC1A
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/sj.ijo.0803228

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 148.2±46.9 vs GG 106.5±51.9 cm 2 , P =0.001; subcutaneous fat: XA 271.8±167.1 vs GG 181.5±78.5 cm 2 , P =0.001). Abdominal (XA 4521.9±1749.6 vs GG 3445.2±1443.4 g, P =0.004), central abdominal (XA 1689.0±524.0 vs GG 1228.5±438.7 g, P <0.0001) and non-abdominal fat (XA 18763.8±8789.4 vs GG 13160.4±4255.3 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 → A) polymorphism is associated with increased total, visceral and subcutaneous body fat.