| Summary: | <p>Abstract</p> <p>Background</p> <p>Variants of uncoupling protein genes <it>UCP1 </it>and <it>UCP2 </it>have been associated with a range of traits. We wished to evaluate contributions of known <it>UCP1 </it>and <it>UCP2 </it>variants to metabolic traits in the Insulin Resistance and Atherosclerosis (IRAS) Family Study.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p><it>UCP1 </it>A-3826G was associated with AIR<sub>g </sub>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 <it>UCP1 </it>expression is reported to be restricted to adipose tissue, RT-PCR indicated that <it>UCP1 </it>is expressed in human pancreas and MIN-6 cells, and immunohistochemistry demonstrated co-localization of UCP1 protein with insulin in human islets. <it>UCP2 </it>A55V was associated with waist circumference (P = 0.045) in AA, and BMI in SA (P = 0.018); and <it>UCP2 </it>G-866A with waist-to-hip ratio in AA (P = 0.016).</p> <p>Conclusion</p> <p>This study suggests a functional variant of <it>UCP1 </it>contributes to the variance of AIR<sub>g </sub>in an AA population; the plausibility of this unexpected association is supported by the novel finding that <it>UCP1 </it>is expressed in islets.</p>
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