The uncoupling protein 2 Ala55Val polymorphism is associated with diabetes mellitus: the CARDIA study.
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 approximately 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 were 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 (12.9% vs 9.2%). 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.


CONCLUSIONS
The VV genotype of the UCP2 polymorphism was positively related to diabetes. It may involve increased insulin resistance in those with impaired glucose homeostasis.
Yu
Xinhua
X
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN 55454, USA.
Jacobs
David R
DR
Schreiner
Pamela J
PJ
Gross
Myron D
MD
Steffes
Michael W
MW
Fornage
Myriam
M
D000328:Adult; D044383:Black People; D001786:Blood Glucose / Q000032:analysis; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005215:Fasting; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance / Q000235:genetics; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D000071246:Uncoupling Protein 2; D044465:White People
D001786:Blood Glucose; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2