Transcription Factor 7-Like 2 (TCF7L2) Is Associated With Gestational Diabetes Mellitus and Interacts With Adiposity to Alter Insulin Secretion in Mexican Americans
- Richard M. Watanabe12,
- Hooman Allayee13,
- Anny H. Xiang1,
- Enrique Trigo4,
- Jaana Hartiala3,
- Jean M. Lawrence5 and
- Thomas A. Buchanan24
- 1Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, the University of Southern California, Los Angeles, California
- 2Department of Physiology and Biophysics, Keck School of Medicine, the University of Southern California, Los Angeles, California
- 3Institute for Genetic Medicine, Keck School of Medicine, the University of Southern California, Los Angeles, California
- 4Division of Endocrinology and Diabetes, Department of Medicine, Keck School of Medicine, the University of Southern California, Los Angeles, California
- 5Research 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
Abstract
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′ Δinsulin (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′ Δinsulin 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 β-cell compensation for insulin resistance based on 30′ Δinsulin 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.
- AIR, acute insulin response
- GDM, gestational diabetes mellitus
- IVGTT, intravenous glucose tolerance test
- LD, linkage disequilibrium
- OGTT, oral glucose tolerance test
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on 22 February 2007. DOI: 10.2337/db06-1682.
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Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db06-1682.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted February 9, 2007.
- Received December 1, 2006.
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