Identification and association of TCF7L2 gene polymorphism with type 2 diabetes risk in north Indian population
Paper Details
Identification and association of TCF7L2 gene polymorphism with type 2 diabetes risk in north Indian population
Abstract
Type 2 diabetes Mellitus (T2DM) is a metabolic disorder caused by increased insulin secretion and high blood glucose levels. These increased glucose levels lead to various complications. Here, we investigate the case-control study, where we have selected 200 diabetic and 200 healthy participants from the North Indian population. To understand the function of the rs4506565 & rs11196205 single-nucleotide polymorphism of the TCF7L2 gene in T2DM, I used amplification refractory mutation system (ARMS-PCR) and DNA sequencing. The analysis of the rs4506565 and rs11196205 polymorphisms showed a significant association with T2DM when comparing patients with controls (p-values < 0.05). The TT genotype of rs4506565 shows a higher frequency in the diabetes group (49%) compared to the control group (32.5%), with a model of T/T vs. A/T-A/A: 𝜒2=12.01, p=0.0008, OR=1.99 and 95% Cl= 1.33-2.99. Similarly, the CC genotype of rs11196205 was more frequent in the diabetes group (51%) compared to the control group (30%), with a model of C/C vs. C/C-G/G: 𝜒2=18.16, p=0.001, OR=0.41, and 95% Cl=0.27- 0.62 in the North Indian population. Overall, our recent findings suggest that rs4506565 and rs11196205 are positively associated with susceptibility to T2DM.
Abdullah A, Ali S. 2021. Assessment of the relationship of transcription factor 7-like 2 rs4506565 (T/A) variant with type 2 diabetes in Iraqi Arab patients. Meta Gene 31. https://doi.org/10.1016/j.mgene.2021.101008
Agostini LdaC, Coelho LFD, Machado e Silva RB, Silva NN T, Lopes ACF, Belo VA, Coura-Vital W, Teixeira LFdM, Lima AA, da Silva GN. 2026. rs11196205 variant in the TCF7L2 gene is associated with an increased cardiovascular risk in individuals with hypertension and diabetes. Archives of Medical Research 57, 103268. https://doi.org/10.1016/j.arcmed.2025.103268
Anjana RM, Unnikrishnan R, Deepa M, Pradeepa R, Tandon N, Das AK, Joshi S, Bajaj S, Jabbar PK, Das HK. 2023. Metabolic non-communicable disease health report of India: The ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17). The Lancet Diabetes & Endocrinology 11, 474–489. https://doi.org/10.1016/S2213-8587(23)00119-5
Badriyya E, Achyar A, Syamsurizal. 2021. Primer design of SNP rs4506565 transcription factor 7 like 2 (TCF7L2) gene to detect type-2 diabetes mellitus. In: Proceedings of the 2nd International Conference on Contemporary Science and Clinical Pharmacy 2021 (ICCSCP 2021). Atlantis Press. pp. 197–202. https://doi.org/10.2991/ahsr.k.211105.029
Badriyya E, Achyar A. 2020. Primer construction to detect SNP rs11196205 transcription factor 7 like 2 (TCF7L2) using amplification refractory mutation system (ARMS) PCR to detect type-2 diabetes mellitus. Bioscience 4, 151. https://doi.org/10.24036/0202042108497-0-00
Chandak GR, Janipalli CS, Bhaskar S, Kulkarni SR, Mohankrishna P, Hattersley AT, Frayling TM, Yajnik CS. 2007. Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population. Diabetologia 50, 63–67. https://doi.org/10.1007/s00125-006-0502-2
Del Bosque-Plata L, Martínez-Martínez E, Espinoza-Camacho MÁ, Gragnoli C. 2021. The role of TCF7L2 in type 2 diabetes. Diabetes 70, 1220–1228. https://doi.org/10.2337/db20-0573
Dewi A, Paramita D, Fachiroh J. 2022. Tetra-primer amplification refractory mutation system (ARMS) PCR used to detect 3’UTR rs1948 mutation in CHRNB4. Indonesian Journal of Biotechnology 27, 1. https://doi.org/10.22146/ijbiotech.64933
Grant SFA, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, Helgason A, Stefansson H, Emilsson V, Helgadottir A, Styrkarsdottir U, Magnusson KP, Walters GB, Palsdottir E, Jonsdottir T, Gudmundsdottir T, Gylfason A, Saemundsdottir J, Wilensky RL, Reilly MP, Rader DJ, Bagger Y, Christiansen C, Gudnason V, Sigurdsson G, Thorsteinsdottir U, Gulcher JR, Kong A, Stefansson K. 2006. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nature Genetics 38, 320–323. https://doi.org/10.1038/ng1732
Gravand A, Foroughmand AM, Boroujeni MP. 2018a. A study on the association of TCF7L2 rs11196205 (C/G) and CAPN10 rs3792267 (G/A) polymorphisms with type 2 diabetes mellitus in the southwestern region of Iran. Egyptian Journal of Medical Human Genetics 19, 403–407. https://doi.org/10.1016/j.ejmhg.2018.01.007
Gravand A, Foroughmand AM, Boroujeni MP. 2018b. A study on the association of TCF7L2 rs11196205 (C/G) and CAPN10 rs3792267 (G/A) polymorphisms with type 2 diabetes mellitus in the southwestern region of Iran. Egyptian Journal of Medical Human Genetics 19, 403–407. https://doi.org/10.1016/j.ejmhg.2018.01.007
Khan SM, El Karte N, El Hajj Chehadeh S, Hassoun A, Afandi B, Tay GK, Alsafar H. 2021. Association between type 2 diabetes mellitus and TCF7L2 gene variants in the Emirati population: Genetics of diabetes in the United Arab Emirates. American Journal of Human Biology 33, e23434. https://doi.org/10.1002/ajhb.23434
Ma CX, Ma XN, Guan CH, Li YD, Mauricio D, Fu SB. 2022. Cardiovascular disease in type 2 diabetes mellitus: Progress toward personalized management. Cardiovascular Diabetology 21, 74. https://doi.org/10.1186/s12933-022-01516-6
Marzi C, Huth C, Kolz M, Grallert H, Meisinger C, Wichmann HE, Rathmann W, Herder C, Illig T. 2007. Variants of the transcription factor 7-like 2 gene (TCF7L2) are strongly associated with type 2 diabetes but not with the metabolic syndrome in the MONICA/KORA surveys. Hormone and Metabolic Research 39, 46–52. https://doi.org/10.1055/s-2007-957345
Miller SA, Dykes DD, Polesky HF. 1988. A simple salting-out procedure for extracting DNA from human nucleated cells. Nucleic Acids Research 16, 1215–1215. https://doi.org/10.1093/nar/16.3.1215
Mitroi AF, Leopa N, Dumitru E, Brînzan C, Tocia C, Dumitru A, Popescu RC. 2022. Association of TCF7L2, CASC8 and GREM1 polymorphisms in patients with colorectal cancer and type II diabetes mellitus. Genes 13. https://doi.org/10.3390/genes13081297
Movahednasab M, Dianat-Moghadam H, Khodadad S, Nedaeinia R, Safabakhsh S, Ferns G, Salehi R. 2025. GLP-1-based therapies for type 2 diabetes: From single, dual and triple agonists to endogenous GLP-1 production and L-cell differentiation. Diabetology & Metabolic Syndrome 17, 60. https://doi.org/10.1186/s13098-025-01623-w
Najmiatul F, Zuhanna FN, Yosmar R. 2023. The relationship of diuretic therapy and clinical outcome on quality of life of patients with congestive heart failure. Malaysian Journal of Public Health Medicine 23, 99–103. https://www.mjphm.org/index.php/mjphm/article/view/1981
Nanditha A, Ma RC, Ramachandran A, Snehalatha C, Chan JC, Chia KS, Shaw JE, Zimmet PZ. 2016. Diabetes in Asia and the Pacific: Implications for the global epidemic. Diabetes Care 39, 472–485. https://doi.org/10.2337/dc15-1536
Peng S, Zhu Y, Lü B, Xu F, Li X, Lai M. 2012. TCF7L2 gene polymorphisms and type 2 diabetes risk: A comprehensive and updated meta-analysis involving 121,174 subjects. Mutagenesis 28, 25–37. https://doi.org/10.1093/mutage/ges048
Pooja S, Shivangi C, Singh S, Raj Modi D. 2025. Interrelation of TCF7L2 gene polymorphism with type 2 diabetes patients of North Indian population. Biochemical and Cellular Archives 25. https://doi.org/10.51470/bca.2025.25.1.000
Rajeev G, CR WDS. 2019. Role of Wnt signaling pathway in type 2 diabetes mellitus: An overview. RGUHS Journal of Medical Sciences 9. https://doi.org/10.26463/rjms.9_4_6
Rathod L, Khan S, Mishra S, Das D, Bora K, Shubham S, Singh S, Kumar M, Tiwari RR, Tiwari A. 2025. Genetic variants and type 2 diabetes in India: A systematic review and meta-analysis of associated polymorphisms in case-control studies. The Lancet Regional Health–Southeast Asia 32. https://doi.org/10.1016/j.lansea.2024.100518
Roden M, Shulman GI. 2019. The integrative biology of type 2 diabetes. Nature 576, 51–60. https://doi.org/10.1038/s41586-019-1797-8
Ruze R, Song J, Yin X, Chen Y, Xu R, Wang C, Zhao Y. 2023. Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: A comprehensive and systematic review. Signal Transduction and Targeted Therapy 8, 139. https://doi.org/10.1038/s41392-023-01376-w
Shi Y, He L. 2005. SHEsis: A powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Research 15, 97–98. https://doi.org/10.1038/sj.cr.7290272
Tian S, Zhao H, Song H. 2024. Shared signaling pathways and targeted therapy by natural bioactive compounds for obesity and type 2 diabetes. Critical Reviews in Food Science and Nutrition 64, 5039–5056. https://doi.org/10.1080/10408398.2022.2148090
Verma S, Srivastava N, Banerjee M. 2021. Genetic polymorphisms in TCF7L2 and PPARG genes and susceptibility to type 2 diabetes mellitus. Meta Gene 28, 100864. https://doi.org/10.1016/j.mgene.2021.100864
Wild S, Roglic G, Green A, Sicree R, King H. 2004. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 27, 1047–1053. https://doi.org/10.2337/diacare.27.5.1047
Willert K, Nusse R. 2012. Wnt proteins. Cold Spring Harbor Perspectives in Biology 4, a007864.
Witka BZ, Oktaviani DJ, Marcellino M, Barliana MI, Abdulah R. 2019. Type 2 diabetes-associated genetic polymorphisms as potential disease predictors. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 12, 2689–2706. https://doi.org/10.2337/diacare.27.5.1047
Wu Y, Ding Y, Tanaka Y, Zhang W. 2014. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. International Journal of Medical Sciences 11, 1185. https://doi.org/10.7150/ijms.10001
Yu M, Qin K, Fan J, Zhao G, Zhao P, Zeng W, Chen C, Wang A, Wang Y, Zhong J, Zhu Y, Wagstaff W, Haydon RC, Luu HH, Ho SC, Lee MJ, Strelzow J, Reid RR, He TC. 2024. The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities. Genes & Diseases 11, 101026. https://doi.org/10.1016/j.gendis.2023.04.042
Pooja, Shubhangi Chaturvedi, Shivangi Singh, Shefali Singh, Dinesh Raj Modi, 2025. Identification and association of TCF7L2 gene polymorphism with type 2 diabetes risk in north Indian population. Int. J. Biomol. Biomed., 21(2), 1-10.
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