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Open Access Research article

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

David Melzer1*, Anna Murray1, Alison J Hurst1, Michael N Weedon1, Stefania Bandinelli2, Anna Maria Corsi3, Luigi Ferrucci4, Guiseppe Paolisso5, Jack M Guralnik6 and Timothy M Frayling1

Author Affiliations

1 Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter, EX2 5DW, UK

2 Laboratory of Clinical Epidemiology, Italian National Research Council on Aging, Geriatrics Department, 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

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BMC Medicine 2006, 4:34  doi:10.1186/1741-7015-4-34

Published: 20 December 2006

Abstract

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.