Volume 31, Issue 2 (May 2020)
Studies in Medical Sciences 2020, 31(2): 107-118 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Gravand A, Narjes Khatoun S S, Foroughmand A M, Mousavi nasab I, Shafidelpour S. Association Study of Transcription Factor 7-like 2 (TCF7L2) Gene Polymorphisms and Haplotypes with Type 2 Diabetes in the South-West of Iran. Studies in Medical Sciences 2020; 31 (2) :107-118
URL: http://umj.umsu.ac.ir/article-1-4889-en.html
URL: http://umj.umsu.ac.ir/article-1-4889-en.html
Abdollah Gravand 
, Shabani Sadr Narjes Khatoun , Ali Mohammad Foroughmand * , Iman Mousavi nasab , Sana Shafidelpour
, Shabani Sadr Narjes Khatoun , Ali Mohammad Foroughmand * , Iman Mousavi nasab , Sana Shafidelpour
PhD, Department of Genetics, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran (Corresponding Author) , foroughmand.a@scu.ac.ir
Abstract: (3588 Views)
Background & Aims: Type 2 diabetes mellitus (T2DM), one of the costliest chronic diseases of our time, is a multifactorial and heterogenic disease with a complex etiology. Among all the T2DM related genes, the SNPs of the transcription factor 7-like 2 (TCF7L2) gene have been recognized as the strongest genetic risk factors for T2DM in different ethnic groups by several studies. The aim of this study was to investigate the possible association between TCF7L2 gene polymorphisms (rs290487, rs11196205, rs7903146, and rs12255372) and the risk of T2DM in a population from Khuzestan province, South-West of Iran.
Materials & Methods: In this case-control association study, we studied 146 patients with T2DM and 146 healthy subjects. Genotyping for rs290487 and rs11196205 were done by Tetra-Primer ARMS-PCR and genotyping for rs7903146 and rs12255372 were carried out using PCR-RFLP. Statistical analyses were carried out using SPSS v.25.
Results: For rs290487 polymorphism, TT and TC genotypes were not observed in patients and controls, and all of the subjects showed only CC genotype. The C allele of rs11196205 polymorphism was associated with T2DM (OR = 1.393, 95% CI = 1.005-1.932, p-value = 0.046). Two other studied polymorphisms, rs7903146 and rs12255372, had no significant differences in the genotype and allele frequencies between the two groups. Three-variant haplotypes of TCF7L2 gene were analyzed using the PHASE software. There was no significant difference between control group and case group for haplotype distribution.
Conclusion: Our results suggest that there is a significant association between rs11196205 polymorphism and T2DM, but no association is observed between the three other polymorphisms (rs290487, rs7903146, and rs12255372) with T2DM in the studied population. Moreover, no risk haplotype is reported in our population.
Materials & Methods: In this case-control association study, we studied 146 patients with T2DM and 146 healthy subjects. Genotyping for rs290487 and rs11196205 were done by Tetra-Primer ARMS-PCR and genotyping for rs7903146 and rs12255372 were carried out using PCR-RFLP. Statistical analyses were carried out using SPSS v.25.
Results: For rs290487 polymorphism, TT and TC genotypes were not observed in patients and controls, and all of the subjects showed only CC genotype. The C allele of rs11196205 polymorphism was associated with T2DM (OR = 1.393, 95% CI = 1.005-1.932, p-value = 0.046). Two other studied polymorphisms, rs7903146 and rs12255372, had no significant differences in the genotype and allele frequencies between the two groups. Three-variant haplotypes of TCF7L2 gene were analyzed using the PHASE software. There was no significant difference between control group and case group for haplotype distribution.
Conclusion: Our results suggest that there is a significant association between rs11196205 polymorphism and T2DM, but no association is observed between the three other polymorphisms (rs290487, rs7903146, and rs12255372) with T2DM in the studied population. Moreover, no risk haplotype is reported in our population.
Keywords: Association study, TCF7L2 gene, Type 2 diabetes mellitus, rs11196205, rs7903146, rs12255372, rs290487, Haplotype
References
1. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 2017;128:40-50. [DOI:10.1016/j.diabres.2017.03.024] [PMID]
2. Esteghamati A, Etemad K, Koohpayehzadeh J, Abbasi M, Meysamie A, Noshad S, et al. Trends in the prevalence of diabetes and impaired fasting glucose in association with obesity in Iran: 2005-2011. Diabetes Res Clin Pract 2014;103:319-27. [DOI:10.1016/j.diabres.2013.12.034] [PMID]
3. Javanbakht M, Mashayekhi A, Baradaran HR, Haghdoost A, Afshin A. Projection of Diabetes Population Size and Associated Economic Burden through 2030 in Iran: Evidence from Micro-Simulation Markov Model and Bayesian Meta-Analysis. PLoS One 2015;10:e0132505. [DOI:10.1371/journal.pone.0132505] [PMID] [PMCID]
4. Gravand A, Foroughmand AM, Pourmehdi Boroujenib M. A study on the association of TCF7L2 rs11196205 (C/G) and CAPN10 rs3792267 (G/A) polymorphisms with type 2 diabetes mellitus in the South Western of Iran. Egypt J Med Hum Genet 2018;19:403-7. [DOI:10.1016/j.ejmhg.2018.01.007]
5. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998;21:1414-31. [DOI:10.2337/diacare.21.9.1414] [PMID]
6. Uma Jyothi K, Jayaraj M, Subburaj KS, Prasad KJ, Kumuda I, Lakshmi V, et al. Association of TCF7L2 gene polymorphisms with T2DM in the population of Hyderabad, India. PLoS One 2013;8:e60212 [DOI:10.1371/journal.pone.0060212] [PMID] [PMCID]
7. Herder C, Roden M. Genetics of type 2 diabetes: pathophysiologic and clinical relevance. Eur J Clin Invest 2011;41:679-92. [DOI:10.1111/j.1365-2362.2010.02454.x] [PMID]
8. Florez JC. The new type 2 diabetes gene TCF7L2. Curr Opin Clin Nutr Metab Care 2007;10:391-6. [DOI:10.1097/MCO.0b013e3281e2c9be] [PMID]
9. Kommoju UJ, Reddy BM. Genetic etiology of type 2 diabetes mellitus: a review. Int J Diabetes Dev Ctries 2011;31:51-64. [DOI:10.1007/s13410-011-0020-8]
10. Billings LK, Florez JC. The genetics of type 2 diabetes: what have we learned from GWAS? Ann N Y Acad Sci 2010;1212:59-77. [DOI:10.1111/j.1749-6632.2010.05838.x] [PMID] [PMCID]
11. Grotz AK, Gloyn AL, Thomsen SK. Prioritising Causal Genes at Type 2 Diabetes Risk Loci. Curr Diab Rep 2017;17:76. [DOI:10.1007/s11892-017-0907-y] [PMID] [PMCID]
12. Acharya S, Al-Elq A, Al-Nafaie A, Muzaheed M, Al-Ali A. Type 2 diabetes mellitus susceptibility gene TCF7L2 is strongly associated with hyperglycemia in the Saudi Arabia Population of the eastern province of Saudi Arabia. Eur Rev Med Pharmacol Sci 2015;19:3100-6. [Google Scholar]
13. Struewing I, Boyechko T, Barnett C, Beildeck M, Byers SW, Mao CD. The balance of TCF7L2 variants with differential activities in Wnt-signaling is regulated by lithium in a GSK3beta-independent manner. Biochem Biophys Res Commun 2010;399:245-50. [DOI:10.1016/j.bbrc.2010.07.062] [PMID] [PMCID]
14. Barros CMAR, Araujo-Neto AP, Lopes TR, Barros MAL, Motta FJN, Canalle R, et al. Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil. Genet Mol Res 2014;13:7889-98. [DOI:10.4238/2014.September.29.1] [PMID]
15. van Amerongen R, Nawijn MC, Lambooij J-P, Proost N, Jonkers J, Berns A. Frat oncoproteins act at the crossroad of canonical and noncanonical Wnt-signaling pathways. Oncogene 2010;29:93-104. [DOI:10.1038/onc.2009.310] [PMID]
16. Pang DX, Smith AJP, Humphries SE. Functional analysis of TCF7L2 genetic variants associated with type 2 diabetes. Nutr Metab Cardiovasc Dis 2013;23:550-6. [DOI:10.1016/j.numecd.2011.12.012] [PMID] [PMCID]
17. Damcott CM, Pollin TI, Reinhart LJ, Ott SH, Shen H, Silver KD, et al. Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish: replication and evidence for a role in both insulin secretion and insulin resistance. Diabetes 2006;55:2654-9. [DOI:10.2337/db06-0338] [PMID]
18. Chang Y-C, Chang T-J, Jiang Y-D, Kuo S-S, Lee K-C, Chiu KC, et al. Association study of the genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene and type 2 diabetes in the Chinese population. Diabetes 2007;56:2631-7. [DOI:10.2337/db07-0421] [PMID]
19. Palizban A, Nikpour M, Salehi R, Maracy M-R. Association of a common variant in TCF7L2 gene with type 2 diabetes mellitus in a Persian population. Clin Exp Med 2012;12:115-9. [DOI:10.1007/s10238-011-0144-7] [PMID]
20. Cauchi S, El Achhab Y, Choquet H, Dina C, Krempler F, Weitgasser R, et al. TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis. J Mol Med (Berl) 2007;85:777-82. [DOI:10.1007/s00109-007-0203-4] [PMID]
21. Peng S, Zhu Y, Lü B, Xu F, Li X, Lai M. TCF7L2 gene polymorphisms and type 2 diabetes risk: a comprehensive and updated meta-analysis involving 121,174 subjects. Mutagenesis 2013;28:25-37. [DOI:10.1093/mutage/ges048] [PMID]
22. Pourahmadi M, Erfanian S, Moradzadeh M, Jahromi AS. Non-Association between rs7903146 and rs12255372 Polymorphisms in Transcription Factor 7-Like 2 Gene and Type 2 Diabetes Mellitus in Jahrom City, Iran. Diabetes Metab J 2015;39:512-7. [DOI:10.4093/dmj.2015.39.6.512] [PMID] [PMCID]
23. Bodhini D, Radha V, Dhar M, Narayani N, Mohan V. The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians. Metabolism 2007;56:1174-8. [DOI:10.1016/j.metabol.2007.04.012] [PMID]
24. Humphries SE, Gable D, Cooper JA, Ireland H, Stephens JW, Hurel SJ, et al. Common variants in the TCF7L2 gene and predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women. J Mol Med (Berl) 2006;84:1005-14. [DOI:10.1007/s00109-006-0108-7] [PMID]
25. Helgason A, Pálsson S, Thorleifsson G, Grant SFA, Emilsson V, Gunnarsdottir S, et al. Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nat Genet 2007;39:218-25. [DOI:10.1038/ng1960] [PMID]
26. Wang J, Hu F, Feng T, Zhao J, Yin L, Li L, et al. Meta-analysis of associations between TCF7L2 polymorphisms and risk of type 2 diabetes mellitus in the Chinese population. BMC Med Genet 2013;14:8. [DOI:10.1186/1471-2350-14-8] [PMID] [PMCID]
27. Shokouhi S, Delpisheh A, Haghani K, Mahdizadeh M, Bakhtiyari S. Association of rs7903146, rs12255372, and rs290487 polymorphisms in TCF7L2 gene with type 2 diabetes in an Iranian Kurdish ethnic group. Clin Lab 2014;60:1269-76. [DOI:10.7754/Clin.Lab.2013.130809] [PMID]
28. Alami FM, Ahmadi M, Bazrafshan H, Tabarraei A, Khosravi A, Tabatabaiefar MA, et al. Association of the TCF7L2 rs12255372 (G/T) variant with type 2 diabetes mellitus in an Iranian population. Genet Mol Biol 2012;35:413-7. [DOI:10.1590/S1415-47572012005000029] [PMID] [PMCID]
29. Amoli MM, Amiri P, Tavakkoly-Bazzaz J, Charmchi E, Hafeziyeh J, Keramatipour M, et al. Replication of TCF7L2 rs7903146 association with type 2 diabetes in an Iranian population. Genet Mol Biol 2010;33:449-51. [DOI:10.1590/S1415-47572010005000056] [PMID] [PMCID]
30. Grant SFA, 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;38:320-3. [DOI:10.1038/ng1732] [PMID]
31. Groves CJ, Zeggini E, Minton J, Frayling TM, Weedon MN, Rayner NW, et al. Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. Diabetes 2006;55:2640-4. [DOI:10.2337/db06-0355] [PMID]
32. Scott LJ, Bonnycastle LL, Willer CJ, Sprau AG, Jackson AU, Narisu N, et al. Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample. Diabetes 2006;55:2649-53. [DOI:10.2337/db06-0341] [PMID]
33. 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;117:2155-63. [] [PMID] [PMCID]
34. Alsmadi O, Al-Rubeaan K, Mohamed G, Alkayal F, Al-Saud H, Al-Saud NA, et al. Weak or no association of TCF7L2 variants with Type 2 diabetes risk in an Arab population. BMC Med Genet 2008;9:72. [] [PMID] [PMCID]
35. Rafati R, Jalal R, Asoodeh A, Matin MM. Association of rs12255372 (TCF7L2) and D76N (PDX-1) Polymorphisms with Type 2 Diabetes in a Population Living in Northeast Iran. Arch Iran Med 2015;18:376-8. [Google Scholar]
36. Hayashi T, Iwamoto Y, Kaku K, Hirose H, Maeda S. Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population. Diabetologia 2007;50:980-4. [DOI:10.1007/s00125-007-0618-z] [PMID]
37. Ng MCY, Tam CHT, Lam VKL, So W-Y, Ma RCW, Chan JCN. Replication and identification of novel variants at TCF7L2 associated with type 2 diabetes in Hong Kong Chinese. J Clin Endocrinol Metab 2007;92:3733-7. [DOI:10.1210/jc.2007-0849] [PMID]
38. Luo Y, Wang H, Han X, Ren Q, Wang F, Zhang X, et al. Meta-analysis of the association between SNPs in TCF7L2 and type 2 diabetes in East Asian population. Diabetes Res Clin Pract 2009;85:139-46. [DOI:10.1016/j.diabres.2009.04.024] [PMID]
39. Kalnina I, Geldnere K, Tarasova L, Nikitina-Zake L, Peculis R, Fridmanis D, et al. Stronger association of common variants in TCF7L2 gene with nonobese type 2 diabetes in the Latvian population. Exp Clin Endocrinol Diabetes 2012;120:466-8. [DOI:10.1055/s-0032-1306298] [PMID]
40. Saravani R, Irani Z, Galavi HR. Evaluation of Transcription Factor 7 like 2 polymorphisms and haplotypes in risk of Type 2 Diabetes. Rev Rom Med Lab 2016;24:423-30. [DOI:10.1515/rrlm-2016-0038]
41. Ren Q, Xiao J, Han X, Luo Y, Yang W, Ji L. Rs290487 of TCF7L2 gene is not associated with type 2 diabetes in Chinese Han population: a case control study and meta-analysis. Exp Clin Endocrinol Diabetes 2013;121:526-30. [DOI:10.1055/s-0033-1347199] [PMID]
42. Miyake K, Horikawa Y, Hara K, Yasuda K, Osawa H, Furuta H, et al. Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects. J Hum Genet 2008;53:174-80. [DOI:10.1007/s10038-007-0231-5] [PMID]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
