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Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population

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Rees, Simon D., Bellary, Srikanth, Britten, Abigail C., O'Hare, J. Paul, Kumar, Sudhesh, Barnett, A. H. (Anthony H.), 1951- and Kelly, M. Ann . (2008) Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population. BMC Medical Genetics, Vol.9 (No.8). ISSN 1471-2350

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Official URL: http://dx.doi.org/10.1186/1471-2350-9-8

Abstract

Background Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry. Methods We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects. Results The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 – 1.56, p = 1.96 × 10-3). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p ≤ 1.04 × 10-7). Conclusion Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups.

Item Type:	Journal Article
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI) Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Diabetes -- Great Britain, Gene mapping, Minorities -- Health and hygiene -- Great Britain, Asians -- Great Britain
Journal or Publication Title:	BMC Medical Genetics
Publisher:	BioMed Central Ltd.
ISSN:	1471-2350
Date:	21 February 2008
Volume:	Vol.9
Number:	No.8
Identification Number:	10.1186/1471-2350-9-8
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
References:	1. 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. 2. Zhang C, Qi L, Hunter DJ, Meigs JB, Manson JE, van Dam RM, Hu FB: Variant of transcription factor 7-like 2 (TCF7L2) gene and the risk of type 2 diabetes in large cohorts of U.S. women and men. Diabetes 2006, 55:2645-2648. 3. Wang J, Kuusisto J, Vanttinen M, Kuulasmaa T, Lindstrom J, Tuomilehto J, Uusitupa M, Laakso M: Variants of transcription factor 7- like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion. Diabetologia 2007, 50:1192-1200. 4. 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. 5. 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. 6. Mayans S, Lackovic K, Lindgren P, Ruikka K, Agren A, Eliasson M, Holmberg D: TCF7L2 polymorphisms are associated with type 2 diabetes in northern Sweden. Eur J Hum Genet 2007, 15:342-346. 7. Humphries SE, Gable D, Cooper JA, Ireland H, Stephens JW, Hurel SJ, Li KW, Palmen J, Miller MA, Cappuccio FP, Elkeles R, Godsland I, Miller GJ, Talmud PJ: 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 2006, 84:1-10. 8. Loos RJ, Franks PW, Francis RW, Barroso I, Gribble FM, Savage DB, Ong KK, O'Rahilly S, Wareham NJ: TCF7L2 polymorphisms modulate proinsulin levels and {beta}-cell function in a British Europid population. Diabetes 2007, 56:1943-1947. 9. Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, Knowler WC, Nathan DM, Altshuler D: TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med 2006, 355:241-250. 10. 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. 11. 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. 12. Florez JC: The new type 2 diabetes gene TCF7L2. Curr Opin Clin Nutr Metab Care 2007, 10:391-396. 13. Cauchi S, El Achhab Y, Choquet H, Christian D, 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. Journal of Molecular Medicine 2007, 85:777-782. 14. Saxena R, Gianniny L, Burtt NP, Lyssenko V, Giuducci C, Sjogren M, Florez JC, Almgren P, Isomaa B, Orho-Melander M, Lindblad U, Daly MJ, Tuomi T, Hirschhorn JN, Ardlie KG, Groop LC, Altshuler D: Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals. Diabetes 2006, 55:2890-2895. 15. Smith U: TCF7L2 and type 2 diabetes-we WNT to know. Diabetologia 2007, 50:5-7. 16. Barnett AH, Dixon AN, Bellary S, Hanif MW, O'Hare JP, Raymond NT, Kumar S: Type 2 diabetes and cardiovascular risk in the UK south Asian community. Diabetologia 2006, 49:2234-2246. 17. WHO Consultation: Definition, Diagnosis and Classification of Diabetes Mellitus and its complications, Part 1: Diagnosis and Classification of Diabetes Mellitus. Report of the WHO Consultation 1999, Geneva:World Health Organisation. 18. Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21:263-265. 19. The International HapMap Consortium: The International Hap- Map Project. Nature 2003, 426:789-796. 20. Cauchi S, Meyre D, Dina C, Choquet H, Samson C, Gallina S, Balkau B, Charpentier G, Pattou F, Stetsyuk V, Scharfmann R, Staels B, Fruhbeck G, Froguel P: Transcription factor TCF7L2 genetic study in the French population: expression in human beta-cells and adipose tissue and strong association with type 2 diabetes. Diabetes 2006, 55:2903-2908. 21. Zhang R, Zhu Z, Zhu H, Nguyen T, Yao F, Xia K, Liang D, Liu C: SNP Cutter: a comprehensive tool for SNP PCR-RFLP assay design. Nucleic Acids Res 2005, 33:W489-W492. 22. Helgason A, Palsson S, Thorleifsson G, Grant SF, Emilsson V, Gunnarsdottir S, Adeyemo A, Chen Y, Chen G, Reynisdottir I, Benediktsson R, Hinney A, Hansen T, Andersen G, Borch-Johnsen K, Jorgensen T, Schafer H, Faruque M, Doumatey A, Zhou J, Wilensky RL, Reilly MP, Rader DJ, Bagger Y, Christiansen C, Sigurdsson G, Hebebrand J, Pedersen O, Thorsteinsdottir U, Gulcher JR, Kong A, Rotimi C, Stefansson K: Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nat Genet 2007, 39:218-225.
URI:	http://wrap.warwick.ac.uk/id/eprint/546