Uncoupling protein 2 Ala55Val polymorphism is associated with a higher acute insulin response to glucose

Willig, Amanda L.; Casazza, Krista R.; Divers, Jasmin; Bigham, Abigail W.; Gower, Barbara A.; Hunter, Gary R.; Fernandez, Jose R.

doi:10.1016/j.metabol.2009.02.016

« Previous Next »Metabolism - Clinical and Experimental
Volume 58, Issue 6 , Pages 877-881, June 2009

Uncoupling protein 2 Ala55Val polymorphism is associated with a higher acute insulin response to glucose

Amanda L. Willig
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL
- Department of Nutrition Sciences and the Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL
- Corresponding author. Department of Nutrition Sciences, WEBB 429, University of Alabama at Birmingham, Birmingham, AL 35294 3360, USA. Tel.: +1 205 975 9678; fax: +1 205 934 7050.
Krista R. Casazza
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL
- Department of Nutrition Sciences and the Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL
Jasmin Divers
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL
- Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL
Abigail W. Bigham
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL
- Department of Preventive Medicine, and Physiology and Biophysics, University of Southern California, Los Angeles, CA
- Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA
Barbara A. Gower
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL
- Department of Nutrition Sciences and the Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL
Gary R. Hunter
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL
- Department of Nutrition Sciences and the Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL
Jose R. Fernandez
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL
- Department of Nutrition Sciences and the Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL
- Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL

Received 21 August 2008; accepted 23 February 2009. published online 15 April 2009.

Abstract

Recent evidence suggests that mitochondrial uncoupling protein 2 (UCP2) in pancreatic β-cells plays a crucial role in insulin production and secretion. We hypothesized that 2 UCP2 polymorphisms, a −55C/T (Ala55Val) substitution in exon 4 and an exon 8 insertion, would alter the acute insulin response to glucose (AIRg). Subjects were 155 African American (AA) and European American (EA) women. Body composition was determined by dual-energy x-ray absorptiometry. Insulin sensitivity and AIRg were measured with an intravenous glucose tolerance test and minimal modeling. To account for the confounding effects of population stratification, estimates of African admixture were obtained from approximately 35 ancestry-informative markers. Uncoupling protein 2 genotyping was conducted with gel electrophoresis. Information was analyzed using mixed linear models. A positive association between the −55C/T homozygous mutation and AIRg was identified in the total sample (P < .01) and independently in EA women (P = .02) but not AA women. The exon 8 insertion did not significantly affect AIRg. No interaction effects of the 2 polymorphisms on AIRg were noted. These results indicate that AIRg is associated with the −55C/T UCP2 homozygous mutation and that the presence of this mutation could alter postchallenge insulin concentration.