Effects of the diabetes linked TCF7L2 polymorphism in a representative older population.
© Melzer et al; licensee BioMed Central Ltd. 2006. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 > or = 65 years from the population representative InCHIANTI study were enrolled in this study. Those with fasting blood glucose of > or = 7 mmol/l or physician diagnosis were considered diabetic. Cut-off points for impaired fasting glucose (IFG) were > or = 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.
This work is supported in part by NIH/NIA grant R01 AG24233-01, and by the Intramural Research Program, National Institute on Aging, NIH. DM is supported by a NHS Executive National Public Health Career Scientist Award, Ref: PHCSA/00/002. The InCHIANTI study was supported as a "targeted project" (ICS 110.1\RS97.71) by the Italian Ministry of Health, by the US National Institute on Aging (Contracts N01-AG-916413, N01-AG-821336 and Contracts 263 MD 9164 13 and 263 MD 821336).
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
This is the final version of the article. Available from BioMed Central via the DOI in this record.
Vol. 4, pp. 34 -
Place of publication