This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 93/1/304    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted 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 Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Palmer, N. D. Articles by Bowden, D. W. Search for Related Content PubMed PubMed Citation Articles by Palmer, N. D. Articles by Bowden, D. W. Related Collections Diabetes and Insulin Metabolism

Association of TCF7L2 Gene Polymorphisms with Reduced Acute Insulin Response in Hispanic Americans

Departments of Biochemistry (N.D.P., A.B.L., D.W.B.), Internal Medicine (D.W.B.), and Public Health Sciences (C.D.L., J.K.C.) and Center for Human Genomics (N.D.P., A.B.L., D.W.B.), Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, Department of Medicine (S.M.H.), University of Texas Health Sciences Center at San Antonio, San Antonio, Texas 78229; Department of Preventive Medicine and Biometrics (J.M.N.), University of Colorado Health Sciences Center, Denver, Colorado 80262; Department of Physiology and Biophysics (R.N.B.), Keck School of Medicine, University of Southern California, Los Angeles, California 90089; and Medical Genetics Institute (M.O.G., J.I.R.), Cedars-Sinai Medical Center, Los Angeles, California 90048

Address all correspondence and requests for reprints to: Donald W. Bowden, Ph.D., Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157. E-mail: dbowden{at}wfubmc.edu.

Context: Genetic variation at the transcription factor 7-like 2 locus has been linked to type 2 diabetes in predominantly European-derived populations. The biological basis of these associations remains to be determined.

Objective: The objective of this study was to evaluate previously associated variants for association with measures of glucose homeostasis in Hispanic-Americans and African-Americans and determine the biological mechanism(s) through which these variants exert their effect.

Design: This study was the Insulin Resistance Atherosclerosis Family Study (IRAS-FS).

Setting: The IRAS-FS is a community-based study of Hispanic-Americans (San Antonio, TX, and San Luis Valley, CO) and African-Americans (Los Angeles, CA).

Participants: A total of 1040 Hispanic-American and 500 African-American individuals from the IRAS-FS formed the basis of this study.

Main Outcomes Measures(s): The primary glucose homeostasis phenotypes of interest in this study were derived from the frequently sampled iv glucose tolerance test and include insulin sensitivity, acute insulin response, and disposition index.

Results: In Hispanic-Americans, significant evidence of association was observed between single-nucleotide polymorphisms rs7903146 and rs112255372 with reduced insulin secretion as measured by acute insulin response and adjusted for the degree of insulin sensitivity (P = 0.032 and 0.036, respectively). Other quantitative measures, e.g. insulin sensitivity or disposition index, were not associated with the single nucleotide polymorphisms examined. In African-Americans there was no evidence of association observed.

Conclusions: These results suggest that transcription factor 7-like 2 variants could play a role in the pathogenesis of type 2 diabetes in the Hispanic-American population through a mechanism involving insulin secretion.