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TCF7L2 Polymorphisms and Progression to Diabetes in the Diabetes Prevention Program
Florez, Jose C.
Jablonski, Kathleen A.
Pollin, Toni I.
de Baker, Paul I.W.
Shuldiner, Alan R.
Knowler, William C.
Nathan, David M.
Altshuler, Alan R.
Article from Journal - ilmiah internasional
The New England Journal of Medicine (keterangan: ada di Proquest) vol. 355 no. 03 (Jul. 2006)
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BACKGROUND Common polymorphisms of the transcription factor 7-like 2 gene (TCF7L2) have recently been associated with type 2 diabetes. We examined whether the two most strongly associated variants (rs12255372 and rs7903146) predict the progression to diabetes in persons with impaired glucose tolerance who were enrolled in the Diabetes Prevention Program, in which lifestyle intervention or treatment with metformin was compared with placebo. METHODS We genotyped these variants in 3548 participants and performed Cox regression analysis using genotype, intervention, and their interactions as predictors. We assessed the effect of genotype on measures of insulin secretion and insulin sensitivity at baseline and at one year. RESULTS Over an average period of three years, participants with the risk-conferring IT genotype at rs7903146 were more likely to have progression from impaired glucose tolerance to diabetes than were CC homozygotes (hazard ratio, 1.55; 95 percent confidence interval, 1.20 to 2.01; P
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