Pilot studies on the prevalence and association of TCF7L2 polymorphisms in non-diabetic participants and type 2 diabetic patients of South Tamil Nadu
DOI:
https://doi.org/10.18203/2394-6040.ijcmph20190528Keywords:
TCF7L2, Genetic predisposition, rs7903146, rs12255372, T2DMAbstract
Background: Genetic predisposition plays a critical role in the incidence of type 2 diabetes mellitus (T2DM). While a few reports strongly associate TCF7L2 gene polymorphisms in the T2DM incidence in India, data pertaining to the prevalence of these polymorphisms in the south Tamil Nadu population has been lacking. Hence, the present study aims to determine the prevalence and association of the TCF7L2 gene variants rs7903146, rs12255372 in the regional population of south Tamil Nadu.
Methods: Peripheral blood samples from controls, T2DM patients were utilized to isolate genomic DNA and genotyping was carried out using PCR based strategies, direct sequencing. Socio-demographic details, anthropometric measurements, determination of postprandial, random blood glucose levels and oral glucose tolerance test (OGTT) were further carried out to evaluate the predisposition risk for T2DM.
Results: 50% of the control group participants and 73.9% of the T2DM patients were positive (CT/TT) for the TCF7L2 polymorphism rs7903146. The rs12255372 SNP was less prevalent in the controls, patients and was dispersed in only 25% of the controls and 60.9% (GT/TT) of the patients. The 60 minutes plasma glucose levels for the oral glucose tolerance test (OGTT) was higher (143.3±19.8) in the rs7903146 and rs12255372 positive control participants.
Conclusions: The study results reveal that TCF7L2 polymorphisms are dispersed in the regional population and further large scale, long term follow up studies will aid preventive and therapeutic measures in T2DM.
References
Bodhini D, Gaal S, Shatwan I, Ramya K, Ellahi B, Surendran S, et al. Interaction between TCF7L2 polymorphism and dietary fat intake on high density lipoprotein cholesterol. PLoS One. 2017;12(11):e0188382.
Khan IA, Poornima S, Jahan P, Rao P, Hasan Q. Type 2 Diabetes Mellitus and the Association of Candidate Genes in Asian Indian Population from Hyderabad, India. J Clin Diagn Res. 2015;9(11):1-5.
Imamura M, Maeda S. Genetics of type 2 diabetes: the GWAS era and future perspectives. Endocr J. 2011;58(9):723-39.
Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445(7130):881-5.
Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, et al. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med. 2006;355(3):241-50.
Saxena R, Hivert MF, Langenberg C, Tanaka T, Pankow JS, Vollenweider P, et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010;42(2):142-8.
Lyssenko V, Lupi R, Marchetti P, Del Guerra S, Orho-Melander M, Almgren P, et al. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest. 2007;117(8):2155-63.
Fernandez-Rhodes L, Howard AG, Graff M, Isasi CR, Highland HM, Young KL, et al. Complex patterns of direct and indirect association between the transcription Factor-7 like 2 gene, body mass index and type 2 diabetes diagnosis in adulthood in the Hispanic Community Health Study/Study of Latinos. BMC Obes. 2018;5:26.
Lu J, Varghese RT, Zhou L, Vella A, Jensen MD. Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146. Metabolism. 2017;68:55-63.
Chandak GR, Janipalli CS, Bhaskar S, Kulkarni SR, Mohankrishna P, Hattersley AT, et al. Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population. Diabetologia. 2007;50(1):63-7.
Chauhan G, Spurgeon CJ, Tabassum R, Bhaskar S, Kulkarni SR, Mahajan A, et al. Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians. Diabetes. 2010;59(8):2068-74.
Sanghera DK, Nath SK, Ortega L, Gambarelli M, Kim-Howard X, Singh JR, et al. TCF7L2 polymorphisms are associated with type 2 diabetes in Khatri Sikhs from North India: genetic variation affects lipid levels. Ann Hum Genet. 2008;72(4):499-509.
Sanghera DK, Ortega L, Han S, Singh J, Ralhan SK, Wander GS, et al. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Med Genet. 2008;9:59.
Vilvanathan S, Gurusamy U, Mukta V, Das AK, Chandrasekaran A. Allele and genotype frequency of a genetic variant in ataxia telangiectasia mutated gene affecting glycemic response to metformin in South Indian population. Indian J Endocrinol Metab. 2014;18(6):850-4.
Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006;38(3):320-3.
Gupta V, Vinay DG, Rafiq S, Kranthikumar MV, Janipalli CS, Giambartolomei C, et al. Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs. Diabetologia. 2012;55(2):349-57.
Mohan V, Goldhaber-Fiebert JD, Radha V, Gokulakrishnan K. Screening with OGTT alone or in combination with the Indian diabetes risk score or genotyping of TCF7L2 to detect undiagnosed type 2 diabetes in Asian Indians. Indian J Med Res. 2011;133:294-9.
Stunkard AJ, Harris JR, Pedersen NL, McClearn GE. The body-mass index of twins who have been reared apart. N Engl J Med. 1990;322(21):1483-7.
Wardle J, Carnell S, Haworth CM, Plomin R. Evidence for a strong genetic influence on childhood adiposity despite the force of the obesogenic environment. Am J Clin Nutr. 2008;87(2):398-404.
Pigeyre M, Yazdi FT, Kaur Y, Meyre D. Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity. Clin Sci (Lond). 2016;130(12):943-86.
Salinas YD, Wang L, DeWan AT. Multiethnic genome-wide association study identifies ethnic-specific associations with body mass index in Hispanics and African Americans. BMC Genet. 2016;17(1):78.
Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197-206.
Dhawan D, Padh H. Genetic variations in TCF7L2 influence therapeutic response to sulfonylureas in Indian diabetics. Diabetes Res Clin Pract. 2016;121:35-40.
Moran Y, Labrador L, Camargo ME, Fernandez D, Chiurillo MA. Design of an allele-specific PCR assay to genotype the rs12255372 SNP in a pilot study of association between common TCF7L2 polymorphisms and type 2 diabetes in Venezuelans. Arch Endocrinol Metab. 2015;60(3):246-51.
Katsoulis K, Paschou SA, Hatzi E, Tigas S, Georgiou I, Tsatsoulis A. TCF7L2 gene variants predispose to the development of type 2 diabetes mellitus among individuals with metabolic syndrome. Epub. 2018;17(3):359-65.
