The association of TCF7L2 rs7903146 polymorphism with type 2 diabetes mellitus among Tatars of Bashkortostan
Diana S. Avzaletdinova,
Leisan F. Sharipova,
Olga V. Kochetova,
Tatyana Vyacheslavovna Morugova,
Vera V. Erdman,
Regina S. Somova,
Olga E. Mustafina https://doi.org/10.14341/DM2004138-45
Abstract
Aim. To perform the analysis of the association of transcription factor 7-like 2 (TCF7L2) gene rs7903146 polymorphism with type 2 diabetes mellitus (T2DM) among Tatars of Bashkortostan.
Materials and methods. In this study, 169 patients with T2DM and 286 controls without clinical symptoms and laboratory signs of diabetes and without diabetes relatives were examined. Amplification of the DNA fragments was performed using real-time polymerase chain reaction (PCR) and TaqMan technique.
Results. Genotype CT and allele T ratios were higher in the T2DM group than in controls (46. 7% vs. 36. 4%, p = 0. 030; 41. 7% vs. 30. 8%, p = 0. 001 respectively). There was a positive association between allele T and T2DM (OR = 1. 61), and allele C had a protective effect (OR = 0. 62, p = 0,001). Carriers of the ТТ genotype had later onset of T2DM (mean = 59. 5 years old) compared with carriers of the CT and CC genotypes (56. 1 years old, p = 0. 044). Basal C-peptide concentration, lipid levels and body mass index were not associated with TCF7L2 rs7903146 polymorphism.
Conclusion. TCF7L2 rs7903146 polymorphism is associated with T2DM among Tatars of Bashkortostan.
About the Authors
Diana S. Avzaletdinova
Bashkir State Medical University, Ufa
Russian Federation
Competing Interests: there is no conflict of interest
Russian Federation
MD, Ph.D., Senior lecturer of Endocrinology department
Competing Interests: there is no conflict of interest
Leisan F. Sharipova
Bashkir State Medical University, Ufa
Russian Federation
MD, Postgraduate student of Endocrinology department
Competing Interests: there is no conflict of interest
Russian Federation
MD, Postgraduate student of Endocrinology department
Competing Interests: there is no conflict of interest
Olga V. Kochetova
Institute of Biochemistry and Genetics of Ufa Scientific Centre of the Russian Academy of Sciences, Ufa
Russian Federation
Ph.D. in Biology, Research associate
Competing Interests: there is no conflict of interest
Russian Federation
Ph.D. in Biology, Research associate
Competing Interests: there is no conflict of interest
Tatyana Vyacheslavovna Morugova
Bashkir State Medical University, Ufa
Russian Federation
MD, PhD, Professor, Chief of Endocrinology department
Competing Interests: there is no conflict of interest
Russian Federation
MD, PhD, Professor, Chief of Endocrinology department
Competing Interests: there is no conflict of interest
Vera V. Erdman
Institute of Biochemistry and Genetics of Ufa Scientific Centre of the Russian Academy of Sciences, Ufa
Russian Federation
PhD in Biology
Russian Federation
PhD in Biology
Regina S. Somova
Institute of Biochemistry and Genetics of Ufa Scientific Centre of the Russian Academy of Sciences, Ufa
Russian Federation
PhD in Biology, Reseach associate
Competing Interests: there is no conflict of interest
Russian Federation
PhD in Biology, Reseach associate
Competing Interests: there is no conflict of interest
Olga E. Mustafina
Institute of Biochemistry and Genetics of Ufa Scientific Centre of the Russian Academy of Sciences, Ufa
Russian Federation
PhD in Biology, Chief of laboratory
Competing Interests: there is no conflict of interest
Russian Federation
PhD in Biology, Chief of laboratory
Competing Interests: there is no conflict of interest
References
1. Medici F, Hawa M, Ianari A, et al. Concordance rate for type II diabetes mellitus in monozygotic twins: actuarial analysis. Diabetologia. 1999;42(2):146-150. doi: 10.1007/s001250051132
2. Yi F, Sun J, Lim GE, et al. Cross talk between the insulin and Wnt signaling pathways: evidence from intestinal endocrine L cells. Endocrinology. 2008;149(5):2341-2351. doi: 10.1210/en.2007-1142
3. Welters HJ, Kulkarni RN. Wnt signaling: relevance to beta-cell biology and diabetes. Trends Endocrinol Metab. 2008;19(10):349-355. doi: 10.1016/j.tem.2008.08.004
4. Duggirala R, Blangero J, Almasy L, et al. Linkage of Type 2 Diabetes Mellitus and of Age at Onset to a Genetic Location on Chromosome 10q in Mexican Americans. Am J Hum Genet. 1999;64(4):1127-1140. doi: 10.1086/302316
5. Reynisdottir I, Thorleifsson G, Benediktsson R, et al. Localization of a susceptibility gene for type 2 diabetes to chromosome 5q34-q35. 2. Am J Hum Genet. 2003;73(2):323-335. doi: 10.1086/377139
6. Grant SF, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006;38(3):320-323. doi: 10.1038/ng1732
7. van Vliet-Ostaptchouk JV, Shiri-Sverdlov R, Zhernakova A, et al. Association of variants of transcription factor 7-like 2 (TCF7L2) with susceptibility to type 2 diabetes in the Dutch Breda cohort. Diabetologia. 2007;50(1):59-62. doi: 10.1007/s00125-006-0477-z.
8. Horikoshi M, Hara K, Ito C, et al. A genetic variation of the transcription factor 7-like 2 gene is associated with risk of type 2 diabetes in the Japanese population. Diabetologia. 2007;50(4):747-751. doi: 10.1007/s00125-006-0588-6
9. Mayans S, Lackovic K, Lindgren P, et al. TCF7L2 polymorphisms are associated with type 2 diabetes in northern Sweden. Eur J Hum Genet. 2007;15(3):342-346. doi: 10.1038/sj.ejhg.5201773
10. Chauhan G, Spurgeon CJ, Tabassum R, 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):2068-2074. doi: 10.2337/db09-1386
11. Ng MC, Saxena R, Li J, et al. Transferability and fine mapping of type 2 diabetes loci in African Americans: the Candidate Gene Association Resource Plus Study. Diabetes. 2013;62(3):965-976. doi: 10.2337/db12-0266
12. Perry JR, Frayling TM. New gene variants alter type 2 diabetes risk predominantly through reduced beta-cell function. Curr Opin Clin Nutr Metab Care. 2008;11(4):371-377. doi: 10.1097/MCO.0b013e32830349a1
13. Yi F, Brubaker PL, Jin T. TCF-4 mediates cell type-specific regulation of proglucagon gene expression by beta-catenin and glycogen synthase kinase-3beta. J Biol Chem. 2005;280(2):1457-1464. doi: 10.1074/jbc.M411487200
14. da Silva Xavier G, Loder MK, McDonald A, et al. TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells. Diabetes. 2009;58(4):894-905. doi: 10.2337/db08-1187
15. Hart LM, Simonis-Bik AM, Nijpels G, et al. Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First-Phase Glucose-Stimulated Insulin Secretion During Hyperglycemic Clamps. Diabetes. 2010;59(1):287-292. doi: 10.2337/db09-0736
16. Lyssenko V, Lupi R, Marchetti P, et al. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest. 2007;117(8):2155-2163. doi: 10.1172/JCI30706
17. Yi F, Brubaker PL, Jin T. TCF-4 mediates cell type-specific regulation of proglucagon gene expression by beta-catenin and glycogen synthase kinase-3beta. J Biol Chem. 2005;280(2):1457-1464. doi: 10.1074/jbc.M411487200
18. Schafer SA, Tschritter O, Machicao F, et al. Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia. 2007;50(12):2443-2450. doi: 10.1007/s00125-007-0753-6
19. Бондарь И.А., Филипенко М.Л., Шабельникова О.Ю., Соколова Е.А. Ассоциация полиморфных маркеров rs7903146 гена TCF7L2 и rs1801282 гена PPARG (Pro12Ala) с сахарным диабетом 2 типа в Новосибирской области // Сахарный диабет. – 2013. – Т. 16. – №4. – C. 17-22. [Bondar’ IA, Filipenko ML, Shabel’nikova OY, Sokolova EA. Rs7903146 variant of TCF7L2 gene and rs18012824 variant of PPARG2 gene (Pro12Ala) are associated with type 2 diabetes mellitus in Novosibirsk population. Diabetes mellitus. 2013;16(4):17-22. (in Russ)] doi: 10.14341/DM2013417-22
20. Никитин А.Г., Потапов В.А., Бровкин А.Н., и др. Ассоциация полиморфных маркеров гена TCF7L2 с сахарным диабетом 2 типа // Клиническая практика. – 2014. – №1. – С. 4-10. [Nikitin AG, Potapov VA, Brovkin AN, et al. association of the polymorphisms of the TCF7L2 genes with type 2 diabetes. 2014;(1):4-10. (in Russ)].
21. Yan Y, North KE, Ballantyne CM, et al. Transcription factor 7-like 2 (TCF7L2) polymorphism and context-specific risk of type 2 diabetes in African American and Caucasian adults: the Atherosclerosis Risk in Communities study. Diabetes. 2009;58(1):285-289. doi: 10.2337/db08-0569
22. Lukacs K, Hosszufalusi N, Dinya E, et al. The type 2 diabetes-associated variant in TCF7L2 is associated with latent autoimmune diabetes in adult Europeans and the gene effect is modified by obesity: a meta-analysis and an individual study. Diabetologia. 2012;55(3):689-693. doi: 10.1007/s00125-011-2378-z
Supplementary files
Review
For citations:
Avzaletdinova D.S., Sharipova L.F., Kochetova O.V., Morugova T.V., Erdman V.V., Somova R.S., Mustafina O.E. The association of TCF7L2 rs7903146 polymorphism with type 2 diabetes mellitus among Tatars of Bashkortostan. Diabetes mellitus. 2016;19(2):119-124. (In Russ.) https://doi.org/10.14341/DM2004138-45
Views:
1276
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
