Diabetes Metab J.  2015 Dec;39(6):512-517. 10.4093/dmj.2015.39.6.512.

Non-Association between rs7903146 and rs12255372 Polymorphisms in Transcription Factor 7-Like 2 Gene and Type 2 Diabetes Mellitus in Jahrom City, Iran

Affiliations
  • 1Department of Anatomy, Jahrom University of Medical Sciences, Jahrom, Iran.
  • 2Research Center for Non-Communicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran. erfanian_85@yahoo.com
  • 3Department of New Sciences and Technology, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

BACKGROUND
Transcription factor 7-like 2 (TCF7L2) is a transcription factor in the Wnt signaling pathway. High levels of TCF7L2 have been reported in most human tissues, including the heart, lung, brain, liver, kidney, placenta, adipose tissues, and pancreatic beta-cells. The purpose of this study was to assess the association between TCF7L2 polymorphisms (rs12255372 and rs7903146) and type 2 diabetes mellitus in the city of Jahrom, Iran.
METHODS
This case-control study was conducted with 200 patients referred to Diabetes Clinics and 200 healthy subjects in Jahrom City. Biochemical characteristics were first determined. TCF7L2 rs1255372 and rs7903146 polymorphisms were then genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.
RESULTS
T-allele frequencies of both single nucleotide polymorphisms (SNPs) were significantly higher in diabetic patients than in normal glucose-tolerant subjects (rs12255372: 20.3% vs. 14.5%; rs7903146: 28.5% vs. 22.25%). The rs12255372 (G/T) polymorphism analysis showed an odds ratio of 0.473 (95% confidence interval [CI], 0.170 to 1.314; P=0.151) for the TT genotype and 0.646 (95% CI, 0.410 to 1.019; P=0.060) for the TG genotype, compared with the GG genotype. The rs7903146 (C/T) polymorphism odds ratios for TT and TC genotypes were 0.564 (95% CI, 0.280 to 1.135; P=0.109) and 0.751 (95% CI, 0.487 to 1.157; P=0.194) compared with the CC genotype, respectively.
CONCLUSION
The rs12255372 and rs7903146 SNPs of the TCF7L2 gene were not associated with insulin resistance in the evaluated population.

Keyword

Diabetes mellitus, type 2; Polymorphisms; rs12255372; rs7903146; TCF7L gene

MeSH Terms

Brain
Case-Control Studies
Diabetes Mellitus, Type 2*
Genotype
Heart
Humans
Insulin Resistance
Iran*
Kidney
Liver
Lung
Odds Ratio
Placenta
Polymorphism, Single Nucleotide
Transcription Factors*
Wnt Signaling Pathway
Transcription Factors

Reference

1. Bloomgarden ZT. Insulin resistance: causes and consequences. Int Rev Neurobiol. 2005; 65:1–24.
2. Kolovou GD, Anagnostopoulou KK, Cokkinos DV. Pathophysiology of dyslipidaemia in the metabolic syndrome. Postgrad Med J. 2005; 81:358–366.
3. Lebovitz HE, Banerji MA. Treatment of insulin resistance in diabetes mellitus. Eur J Pharmacol. 2004; 490:135–146.
4. Olivier M, Hsiung CA, Chuang LM, Ho LT, Ting CT, Bustos VI, Lee TM, De Witte A, Chen YD, Olshen R, Rodriguez B, Wen CC, Cox DR. Single nucleotide polymorphisms in protein tyrosine phosphatase 1beta (PTPN1) are associated with essential hypertension and obesity. Hum Mol Genet. 2004; 13:1885–1892.
5. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. 1991; 14:173–194.
6. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005; 365:1333–1346.
7. Tuomilehto J, Podar T, Tuomilehto-Wolf E, Virtala E. Evidence for importance of gender and birth cohort for risk of IDDM in offspring of IDDM parents. Diabetologia. 1995; 38:975–982.
8. Barnett AH, Eff C, Leslie RD, Pyke DA. Diabetes in identical twins. A study of 200 pairs. Diabetologia. 1981; 20:87–93.
9. Olmos P, A'Hern R, Heaton DA, Millward BA, Risley D, Pyke DA, Leslie RD. The significance of the concordance rate for type 1 (insulin-dependent) diabetes in identical twins. Diabetologia. 1988; 31:747–750.
10. Klein BE, Klein R, Moss SE, Cruickshanks KJ. Parental history of diabetes in a population-based study. Diabetes Care. 1996; 19:827–830.
11. Grant SF, 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. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006; 38:320–323.
12. Ip W, Chiang YT, Jin T. The involvement of the wnt signaling pathway and TCF7L2 in diabetes mellitus: the current understanding, dispute, and perspective. Cell Biosci. 2012; 2:28.
13. Florez JC. The new type 2 diabetes gene TCF7L2. Curr Opin Clin Nutr Metab Care. 2007; 10:391–396.
14. Lyssenko V, Lupi R, Marchetti P, Del Guerra S, Orho-Melander M, Almgren P, Sjogren M, Ling C, Eriksson KF, Lethagen AL, Mancarella R, Berglund G, Tuomi T, Nilsson P, Del Prato S, Groop L. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest. 2007; 117:2155–2163.
15. Chandak GR, Janipalli CS, Bhaskar S, Kulkarni SR, Mohankrishna P, Hattersley AT, Frayling TM, Yajnik CS. Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population. Diabetologia. 2007; 50:63–67.
16. Groves CJ, Zeggini E, Minton J, Frayling TM, Weedon MN, Rayner NW, Hitman GA, Walker M, Wiltshire S, Hattersley AT, McCarthy MI. 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; 55:2640–2644.
17. van Vliet-Ostaptchouk JV, Shiri-Sverdlov R, Zhernakova A, Strengman E, van Haeften TW, Hofker MH, Wijmenga C. Association of variants of transcription factor 7-like 2 (TCF7L2) with susceptibility to type 2 diabetes in the Dutch Breda cohort. Diabetologia. 2007; 50:59–62.
18. Damcott CM, Pollin TI, Reinhart LJ, Ott SH, Shen H, Silver KD, Mitchell BD, Shuldiner AR. 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; 55:2654–2659.
19. Scott LJ, Bonnycastle LL, Willer CJ, Sprau AG, Jackson AU, Narisu N, Duren WL, Chines PS, Stringham HM, Erdos MR, Valle TT, Tuomilehto J, Bergman RN, Mohlke KL, Collins FS, Boehnke M. Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample. Diabetes. 2006; 55:2649–2653.
20. 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; 50:980–984.
21. Cauchi S, El Achhab Y, Choquet H, Dina C, Krempler F, Weitgasser R, Nejjari C, Patsch W, Chikri M, Meyre D, Froguel P. TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis. J Mol Med (Berl). 2007; 85:777–782.
22. Chang YC, Chang TJ, Jiang YD, Kuo SS, Lee KC, Chiu KC, Chuang LM. 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; 56:2631–2637.
23. Guo T, Hanson RL, Traurig M, Muller YL, Ma L, Mack J, Kobes S, Knowler WC, Bogardus C, Baier LJ. TCF7L2 is not a major susceptibility gene for type 2 diabetes in Pima Indians: analysis of 3,501 individuals. Diabetes. 2007; 56:3082–3088.
24. Saadi H, Nagelkerke N, Carruthers SG, Benedict S, Abdulkhalek S, Reed R, Lukic M, Nicholls MG. Association of TCF7L2 polymorphism with diabetes mellitus, metabolic syndrome, and markers of beta cell function and insulin resistance in a population-based sample of Emirati subjects. Diabetes Res Clin Pract. 2008; 80:392–398.
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