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Background  Variants of uncoupling protein genes  UCP1  and  UCP2  have been associated with a range of traits. We wished to evaluate contributions of known  UCP1  and  UCP2  variants to metabolic traits in the Insulin Resistance and Atherosclerosis (IRAS) Family Study.    Methods  We genotyped five promoter or coding single nucleotide polymorphisms (SNPs) in 239 African American (AA) participants and 583 Hispanic participants from San Antonio (SA) and San Luis Valley. Generalized estimating equations using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation were computed for the test of genotypic association, and dominant, additive and recessive models. Tests were adjusted for age, gender and BMI (glucose homeostasis and lipid traits), or age and gender (obesity traits), and empirical P-values estimated using a gene dropping approach.    Results   UCP1  A-3826G was associated with AIR g  in AA (P = 0.006) and approached significance in Hispanic families (P = 0.054); and with HDL-C levels in SA families (P = 0.0004). Although  UCP1  expression is reported to be restricted to adipose tissue, RT-PCR indicated that  UCP1  is expressed in human pancreas and MIN-6 cells, and immunohistochemistry demonstrated co-localization of UCP1 protein with insulin in human islets.  UCP2  A55V was associated with waist circumference (P = 0.045) in AA, and BMI in SA (P = 0.018); and  UCP2  G-866A with waist-to-hip ratio in AA (P = 0.016).    Conclusion  This study suggests a functional variant of  UCP1  contributes to the variance of AIR g  in an AA population; the plausibility of this unexpected association is supported by the novel finding that  UCP1  is expressed in islets.

bmc endocrine disorders

The uncoupling protein 1 gene, UCP1, is expressed in mammalian islet cells and associated with acute insulin response to glucose in African American families from the IRAS Family Study