HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix All Versions of this Article: db06-1682v1 56/5/1481    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Watanabe, R. M. Articles by Buchanan, T. A. Search for Related Content PubMed PubMed Citation Articles by Watanabe, R. M. Articles by Buchanan, T. A. Social Bookmarking                What's this?

Transcription Factor 7-Like 2 (TCF7L2) Is Associated With Gestational Diabetes Mellitus and Interacts With Adiposity to Alter Insulin Secretion in Mexican Americans

¹ Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, the University of Southern California, Los Angeles, California
² Department of Physiology and Biophysics, Keck School of Medicine, the University of Southern California, Los Angeles, California
³ Institute for Genetic Medicine, Keck School of Medicine, the University of Southern California, Los Angeles, California
⁴ Division of Endocrinology and Diabetes, Department of Medicine, Keck School of Medicine, the University of Southern California, Los Angeles, California
⁵ Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California

Address correspondence and reprint requests to Richard M. Watanabe, PhD, Department of Preventive Medicine, Keck School of Medicine of USC, 1540 Alcazar St., CHP-220, Los Angeles, CA 90089-9011. E-mail: rwatanab{at}usc.edu

Abbreviations: AIR, acute insulin response; GDM, gestational diabetes mellitus; IVGTT, intravenous glucose tolerance test; LD, linkage disequilibrium; OGTT, oral glucose tolerance test

OBJECTIVE— Variation in transcription factor 7-like 2 (TCF7L2) gene has been shown to be associated with type 2 diabetes and diabetes-related quantitative traits. We examined variation in a 0.1-Mb region surrounding marker DG10S478 for association with diabetes-related quantitative traits in 132 Mexican-American families of a proband with previous gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS— Study participants were phenotyped by an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test and by a dual-energy X-ray absorptiometry scan for percentage of body fat. Of the 42 tag single nucleotide polymorphisms (SNPs) genotyped, 15 were identified.

RESULTS— On univariate analysis, none of the SNPs showed association with diabetes-related quantitative traits. However, rs12255372 showed association with 30' insulin (OGTT 30' min fasting insulin) in an interaction with percentage of body fat (Bonferroni-corrected P = 0.027). The effect of adiposity to increase 30' insulin was greater in subjects with the T allele. This interaction was not associated with acute insulin response to intravenous glucose. rs12255372 also showed an association with ß-cell compensation for insulin resistance based on 30' insulin in an interaction with percentage of body fat (Bonferroni-corrected P = 0.014). rs12255372 was also associated with GDM (odds ratio [OR] 2.49 [95% CI 1.17–5.31]; P = 0.018) in our case-control sample.

CONCLUSIONS— We conclude that variation in TCF7L2 is associated with GDM and interacts with adiposity to alter insulin secretion in Mexican Americans. Our observations partly explain the increased ORs observed in previous associated studies when analyses were restricted to lean subjects and the variability in quantitative trait association results.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. O. Goodarzi and J. I. Rotter Testing the Gene or Testing a Variant?: The Case of TCF7L2 Diabetes, October 1, 2007; 56(10): 2417 - 2419. [Full Text] [PDF]