Effects of the diabetes linked TCF7L2 polymorphism in a representative older population

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• 作者：David Melzer (1)
  Anna Murray (1)
  Alison J Hurst (1)
  Michael N Weedon (1)
  Stefania Bandinelli (2)
  Anna Maria Corsi (3)
  Luigi Ferrucci (4)
  Guiseppe Paolisso (5)
  Jack M Guralnik (6)
  Timothy M Frayling (1)
  
• 刊名：BMC Medicine
• 出版年：2006
• 出版时间：December 2006
• 年：2006
• 卷：4
• 期：1
• 全文大小：513KB
• 参考文献：1. Wray LA, Ofstedal MB, Langa KM, Blaum CS: The effect of diabetes on disability in middle-aged and older adults. / J Gerontol A Biol Sci Med Sci 2005, 60:1206-211.
  2. Beckman JA, Creager MA, Libby P: Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. / JAMA 2002, 287:2570-581. CrossRef
  3. Costa J, Borges M, David C, Vaz Carneiro A: Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients: meta-analysis of randomised controlled trials. / BMJ 2006, 332:1115-124. CrossRef
  4. 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, 38:320-23. CrossRef
  5. Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, Knowler WC, Nathan DM, Altshuler D, the Diabetes Prevention Program Research Group: TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. / N Engl J Med 2006, 355:241-50. CrossRef
  6. Cauchi S, Meyre D, Dina C, Choquet H, Samson C, Gallina S, Balkau B, Charpentier G, Pattou F, Stetsyuk V, Scharfmann R, Staels B, Frühbeck 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, 55:2903-908. CrossRef
  7. 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, 55:2890-895. CrossRef
  8. 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, 55:2654-659. CrossRef
  9. 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, 55:2649-653. CrossRef
  10. 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, 55:2645-648. CrossRef
  11. 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, 55:2640-644. CrossRef
  12. Sackett DL, Haynes RB: The architecture of diagnostic research. / BMJ 2002, 324:539-41. CrossRef
  13. Hattersley AT, Pearson ER: Minireview: pharmacogenetics and beyond: the interaction of therapeutic response, beta-cell physiology, and genetics in diabetes. / Endocrinology 2006, 147:2657-663. CrossRef
  14. Ferrucci L, Bandinelli S, Benvenuti E, Di Iorio A, Macchi C, Harris TB, Guralnik JM: Subsystems contributing to the decline in ability to walk: bridging the gap between epidemiology and geriatric practice in the InCHIANTI study. / JAGS 2000, 48:1618-625.
  15. Zuliani G, Volpato S, Ble A, Bandinelli S, Corsi AM, Lauretani F, Paolisso G, Fellin R, Ferrucci L: High interleukin-6 plasma levels are associated with low HDL-C levels in community-dwelling older adults: the InChianti study. / Atherosclerosis 2006, / in press.
  16. Ferrucci L, Guralnik JM, Woodman RC, Bandinelli S, Lauretani F, Corsi AM, Chaves P, Ershler W, Longo D: Proinflammatory state and circulating erythropoietin in persons with and without anemia. / Am J Med 2005, 118:1288. CrossRef
  17. Kahn R: Report of the expert committee on the diagnosis and classification of diabetes mellitus. / Diabetes Care 1997, 20:1183-197.
  18. Kahn R: Follow-up report on the diagnosis of diabetes mellitus. / Diabetes Care 2003, 26:3160-167. CrossRef
  19. Ble A, Fink JC, Woodman RC, Klausner MA, Windham BG, Guralnik JM, Ferrucci L: Renal function, erythropoietin, and anemia of older persons: the InCHIANTI study. / Arch Intern Med 2005, 165:2222-227. CrossRef
  20. National Institutes of Health: / Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Executive Summary (NIH publ. no. 01-670) Bethesda, MD: National Institutes of Health, National Heart, Lung and Blood Institute 2001.
  21. Weedon MN, McCarthy MI, Hitman G, Walker M, Groves CJ, Zeggini E, Rayner NW, Shields B, Owen KR, Hattersley AT, Frayling TM: Combining information from common type 2 diabetes risk polymorphisms improves disease prediction. / PLoS Med 2006,3(10):e374. CrossRef
  22. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P: Risk of dementia in diabetes mellitus: a systematic review. / Lancet Neurology 2006, 5:64-4. CrossRef
  23. Elahi D, Muller DC, Egan JM, Andres R, Veldhuis J, Meneilly GS: Glucose tolerance, glucose utilization and insulin secretion in ageing. / Novartis Foundation Symposium 2002, 242:222-46. CrossRef
  24. Turner RC, Millns H, Neil HAW, Stratton IM, Manley SE, Matthews DR, Holman RR: Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS: 23). / BMJ 1998, 316:823-28.
  25. Betteridge DJ: Diabetic dyslipidaemia: past, present and future. / Practical Diabetes International 2004, 21:78-5. CrossRef
  26. Hobbs FR: Reducing cardiovascular risk in diabetes: Beyond glycemic and blood pressure control. / Int J Cardiology 2006, 110:137-45. CrossRef
  27. Aiello LM: Perspectives on diabetic retinopathy. / Am J Ophthalmol 2003, 136:122-35. CrossRef
  28. Raptis AE, Viberti G: Pathogenesis of diabetic nephropathy. / Exp Clin Endocrinol Diabetes 2001, 109:S424-S437. CrossRef
  29. Sheetz MJ, King GL: Molecular understanding of hyperglycemia's adverse effects for diabetic complications. / JAMA 2002, 288:2579-588. CrossRef
  30. Turner R: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). / Lancet 1998, 352:837-53. CrossRef
  31. Setter SM, Campbell RK, Cahoon CJ: Biochemical pathways for microvascular complications of diabetes mellitus. / Ann Pharmacother 2003, 37:1858-866. CrossRef
  32. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/4/34/prepub
  
• 作者单位：David Melzer (1)
  Anna Murray (1)
  Alison J Hurst (1)
  Michael N Weedon (1)
  Stefania Bandinelli (2)
  Anna Maria Corsi (3)
  Luigi Ferrucci (4)
  Guiseppe Paolisso (5)
  Jack M Guralnik (6)
  Timothy M Frayling (1)
  
  1. RD&E Wonford Site, Peninsula Medical School, EX2 5DW, Barrack Road, Exeter, UK
  2. Laboratory of Clinical Epidemiology,Geriatrics Department, Italian National Research Council on Aging, Florence, Italy
  3. Tuscany Regional Health Agency, Firenze, Italy, I.O.T. and Department of Medical and Surgical Critical Care, University of Florence, Italy
  4. Longitudinal Studies Section, Clinical Research Branch, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland, USA
  5. Department of Geriatric Medicine and Metabolic Disease, University of Naples, Naples, Italy
  6. Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, Maryland, USA
  

文摘

Background A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene has been found to be associated with type 2 diabetes in case-control studies. We aimed to estimate associations of the marker rs7903146 (C/T) polymorphism with fasting glucose, lipids, diabetes prevalence and complications in an older general population. Methods In total, 944 subjects aged ?65 years from the population representative InCHIANTI study were enrolled in this study. Those with fasting blood glucose of ?7 mmol/l or physician diagnosis were considered diabetic. Cut-off points for impaired fasting glucose (IFG) were ?5.6 mmol/l to < 7 mmol/l. Results In the general population sample, minor (T) allele carriers of rs7903146 had higher fasting blood glucose (FBG) (p = 0.028) but lower fasting insulin (p = 0.030) and HOMA2b scores (p = 0.001), suggesting poorer beta-cell function. T allele carriers also had smaller waist circumference (p = 0.009), lower triglyceride levels (p = 0.006), and higher high-density lipoprotein cholesterol (p = 0.008). The prevalence of diabetes or IFG was 32.4% in TT carriers and 23.3% in CC carriers; adjusted OR = 1.67 (95% confidence interval 1.05 to 2.65, p = 0.031). Within the diabetic and IFG groups, fewer T allele carriers had metabolic syndrome features (p = 0.047) or had experienced a myocardial infarction (p = 0.037). Conversely, T allele carriers with diabetes had poorer renal function (reduced 24-hour creatinine clearance, p = 0.013), and possibly more retinopathy (p = 0.067). Physician-diagnosed dementia was more common in the T carriers (in diabetes p = 0.05, with IFG p = 0.024). Conclusion The TCF7L2 rs7903146 polymorphism is associated with lower insulin levels, smaller waist circumference, and lower risk lipid profiles in the general elderly population. Patients with diabetes who are carriers of the minor allele are less likely to have metabolic-syndrome features, but may experience more microvascular complications, although the number of cases was small. If replicated, these findings may have implications for developing treatment approaches tailored by genotype.