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 148.2±46.9 vs GG 106.5±51.9 cm2, P=0.001; subcutaneous fat: XA 271.8±167.1 vs GG 181.5±78.5 cm2, 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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Mohan V, Shanthirani S, Deepa R, Premalatha G, Sastry NG, Saroja R . Chennai Urban Population Study (CUPS No. 4). Intra-urban differences in the prevalence of the metabolic syndrome in southern India – the Chennai Urban Population Study (CUPS No. 4). Diabet Med 2001; 18: 280–287.
Despres JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C . Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 1990; 10: 497–511.
Mohan V, Sharp PS, Cloke HR, Burrin JM, Schumer B, Kohner EM . Serum immunoreactive insulin responses to a glucose load in Asian Indian and European type 2 (non-insulin-dependent) diabetic patients and control subjects. Diabetologia 1986; 29: 235–237.
Sharp PS, Mohan V, Levy JC, Mather HM, Kohner EM . Insulin resistance in patients of Asian Indian and European origin with non-insulin dependent diabetes. Horm Metab Res 1987; 19: 84–85.
Misra A, Vikram NK . Insulin resistance syndrome (metabolic syndrome) and Asian Indians. Curr Sci 2002; 83: 1483–1496.
Chandalia M, Abate N, Garg A, Stray-Gundersen J, Grundy SM . Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endocrinol Metab 1999; 84: 2329–2335.
Ramachandran A, Snehalatha C, Viswanathan V, Viswanathan M, Haffner SM . Risk of noninsulin dependent diabetes mellitus conferred by obesity and central adiposity in different ethnic groups: a comparative analysis between Asian Indians, Mexican Americans and Whites. Diabetes Res Clin Pract 1997; 36: 121–125.
Joshi SR . Metabolic syndrome – emerging clusters of the Indian phenotype. J Assoc Physicians India 2003; 51: 445–446.
McKeigue PM, Pierpoint T, Ferrie JE, Marmot MG . Relationship of glucose intolerance and hyperinsulinaemia to body fat pattern in south Asians and Europeans. Diabetologia 1992; 35: 785–791.
Pradeepa R, Mohan V . The changing scenario of the diabetes epidemic: implications for India. Indian J Med Res 2002; 116: 121–132.
Raji A, Seely EW, Arky RA, Siminson DC . Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians. J Clin Endocrinol Metab 2001; 86: 5366–5371.
Carey DG, Jenkins AB, Campbell LV, Freund J, Chrisholm DJ . Abdominal fat and insulin resistance in normal and overweight women: direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes 1996; 45: 633–638.
Anjana M, Sandeep S, Deepa R, Vimaleswaran KS, Farooq S, Mohan V . Visceral and central abdominal fat and anthropometry in relation to diabetes in Asian Indians. Diabetes Care 2004; 27: 2948–2953.
Katzmarzyk PT, Perusse L, Bouchard C . Genetics of abdominal visceral fat levels. Am J Hum Biol 1999; 11: 225–235.
Bouchard C, Rice T, Lemieux S, Despres JP, Perusse L, Rao DC . Major gene for abdominal visceral fat area in the Quebec Family Study. Int J Obes Relat Metab Disord 1996; 20: 420–427.
Rice T, Despres JP, Perusse L, Gagnon J, Leon AS, Skinner JS et al. Segregation analysis of abdominal visceral fat: the heritage family study. Obes Res 1997; 5: 417–424.
Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM . A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998; 92: 829–839.
Puigserver P, Spiegelman BM . Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PPARGC1A alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 2003; 24: 78–90.
Attie AD, Kendziorski CM . PPARGC1Aalpha at the crossroads of type 2 diabetes. Nat Genet 2003; 34: 244–245.
Pratley RE, Thompson DB, Prochazka M, Baier L, Mott D, Ravussin E et al. An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians. J Clin Invest 1998; 101: 757–764.
Perusse L, Rice T, Chagnon YC, Despres JP, Lemieux S, Roy S et al. A genome-wide scan for abdominal fat assessed by computed tomography in the Quebec Family Study. Diabetes 2001; 50: 614–621.
Esterbauer H, Oberkofler H, Linnemayr V, Iglseder B, Hedegger M, Wolfsgruber P et al. Peroxisome proliferator-activated receptor-gamma coactivator-1 gene locus: associations with obesity indices in middle-aged women. Diabetes 2002; 51: 1281–1286.
Vimaleswaran KS, Radha V, Ghosh S, Majumder PP, Deepa R, Babu HN et al. Peroxisome proliferator activated receptor gamma coactivator-1 alpha (PGC-1α) gene polymorphisms and their relationship to type 2 diabetes in Asian Indians. Diabetic Med 2005; 1516–1521.
Deepa M, Pradeepa R, Rema M, Mohan A, Deepa R, Shanthirani S et al. The Chennai Urban Rural Epidemiology study (CURES) – study design and methodology (urban component) (CURES-1). J Assoc Physicians India 2003; 51: 863–870.
Regional office for the western pacific of the world health organization. The Asia Pacific perspective: Redefining obesity its treatment. World Health Organization, international association for the study of obesity and International obesity task force, Health Communications Australia Pvt Limited, 2000. pp 22–29.
Carey DG, Jenkins AB, Campbell LV, Freund J, Chisholm DJ . Abdominal fat and insulin resistance in normal and overweight women: direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes 1996; 45: 633–638.
Maniatis T, Fritsch EF, Sambrook J . Molecular Cloning, A Laboratory Manual, 1st edn. Cold Spring Harbor Laboratory: New York, 1982.
Hara K, Tobe K, Okada T, Kadowaki H, Akanuma Y, Ito C . A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to type II diabetes. Diabetologia 2002; 45: 740–743.
Ek J, Andersen G, Urhammer SA, Gaede PH, Drivsholm T, Borch-Johnsen K et al. Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to type II diabetes mellitus. Diabetologia 2001; 44: 2220–2225.
McLachlan GJ, Krishnan T . The EM Algorithm and Extensions: Wiley Series in Probability and Statistics. John Wiley and Sons: New York, 1997.
Mohan V, Deepa R, Rani SS, Premalatha G . Chennai Urban Population Study (CUPS No. 5). Prevalence of coronary artery disease and its relationship to lipids in a selected population in South India: the Chennai Urban Population Study (CUPS No. 5). J Am Coll Cardiol 2001; 38: 682–687.
Maffiuletti NA, Agosti F, Marinone PG, Silvestri G, Lafortuna CL, Sartorio A . Changes in body composition, physical performance and cardiovascular risk factors after a 3-week integrated body weight reduction program and after 1-y follow-up in severely obese men and women. Eur J Clin Nutr 2005; 16 (Epub ahead of print).
Boden G, Homko C, Mozzoli M, Showe LC, Nichols C, Cheung P . Thiazolidinediones upregulate fatty acid uptake and oxidation in adipose tissue of diabetic patients. Diabetes 2005; 54: 880–885.
Baier LJ, Permana PA, Yang X, Pratley RE, Hanson RL, Shen G-Q et al. A calpain-10 gene polymorphism is associated with reduced musle mRNA levels and insulin resistance. J Clin Invest 2000; 106: R69–R73.
Alhopuro P, Katajisto P, Lehtonen R, Ylisaukko-oja SK, Näätsaari L, Karhu A et al. Mutation analysis of three genes encoding novel LKB1-interacting proteins, BRG1, STRADa, and MO25a, in Peutz–Jeghers syndrome. Br J Cancer 2005 (Epub ahead of print).
Fernandez-Cadenas I, Andreu AL, Gamez J, Gonzalo R, Martin MA, Rubio JC et al. Splicing mosaic of the myophosphorylase gene due to a silent mutation in McArdle disease. Neurology 2003; 61: 1432–1434.
Acknowledgements
This study was supported by a grant from the Department of Biotechnology (DBT), Government of India. The CURES field studies were supported by the Chennai Willingdon Corporate Foundation, Chennai. We thank Dr R Emmanuel and colleagues of M/s Bharat Scans for their help with the CT and DXA scans. We thank the epidemiology team of Madras Diabetes Research foundation, Chennai for their help in this study. This is the 20th publication from CURES (CURES-20).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Vimaleswaran, K., Radha, V., Anjana, M. et al. Effect of polymorphisms in the PPARGC1A gene on body fat in Asian Indians. Int J Obes 30, 884–891 (2006). https://doi.org/10.1038/sj.ijo.0803228
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0803228
Keywords
This article is cited by
-
Engineered allele substitution at PPARGC1A rs8192678 alters human white adipocyte differentiation, lipogenesis, and PGC-1α content and turnover
Diabetologia (2023)
-
Genomic analysis to screen potential genes and mutations in children with non-syndromic early onset severe obesity: a multicentre study in Turkey
Molecular Biology Reports (2022)
-
Associations among perfluorooctanesulfonic/perfluorooctanoic acid levels, nuclear receptor gene polymorphisms, and lipid levels in pregnant women in the Hokkaido study
Scientific Reports (2021)
-
Genetics of obesity and its measures in India
Journal of Genetics (2018)
-
Gene expression profiling of the peripheral blood mononuclear cells of offspring of one type 2 diabetic parent
International Journal of Diabetes in Developing Countries (2016)