Received on November 3, 2004
Accepted on May 20, 2005

Lipids, Lipoproteins, and Cardiovascular Risk Factors

The Uncoupling Protein 2 Ala55Val Polymorphism Is Associated with Diabetes Mellitus: The CARDIA Study

¹ Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN
² Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN, and Department of Nutrition, University of Oslo, Oslo, Norway
³ Department of Laboratory Medicine, Medical School, University of Minnesota, Minneapolis, MN
⁴ Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX

^* To whom correspondence should be addressed. E-mail: jacobs{at}epi.umn.edu.

Background: Uncoupling proteins (UCPs) reduce ATP generation with concomitant increased release of heat. The activities of UCPs have been related to obesity and energy metabolism.

Methods: We investigated the association of the commonly observed UCP2 Ala55Val (V) polymorphism with diabetes mellitus and impaired fasting glucose (IFG) among 3684 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Results: The V frequency was 45% in blacks and 42% in whites. Those with the Val/Val (VV) genotype had a higher incidence of diabetes than those having the Ala/Ala (AA) genotype (5.8% vs 3.3%; P = 0.02). Similarly, the incidences of diabetes in participants without abdominal obesity 2.8% and 1.0% (P = 0.03) in the VV and AA groups, and 12.4% and 8.3% (P = 0.15) in participants with abdominal obesity. The incidence of IFG was higher in VV vs AA only in those without abdominal obesity (13.9% vs 9.4%). These trends persisted in minimally and fully adjusted models, and in strata of blacks and whites and men and women. The homeostasis model assessment for insulin resistance was highest in VV in the combined group of those with IFG or untreated diabetes, but not in those with normal fasting glucose.

Conclusion: The VV genotype of the UCP2 polymorphism was positively related to diabetes. It may involve increased insulin resistance in those with impaired glucose homeostasis.