Research article

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

Michèle M Sale^1,2,3 , Fang-Chi Hsu⁴ , Nicholette D Palmer^1,5 , Candace J Gordon¹ , Keith L Keene¹ , Hermina M Borgerink⁶ , Arun J Sharma⁷ , Richard N Bergman⁸ , Kent D Taylor⁹ , Mohammed F Saad¹⁰ and Jill M Norris¹¹

¹Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, USA

²Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, USA

³Center for Public Health Genomics and Department of Medicine, University of Virginia, Charlottesville, USA

⁴Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, USA

⁵Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, USA

⁶Department of Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, USA

⁷Joslin Diabetes Center and Harvard Medical School, Boston, USA

⁸Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California School of Medicine, Los Angeles, USA

⁹Medical Genetics Institute, and Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, USA

¹⁰Department of Preventive Medicine, Stony Brook School of Medicine, Stony Brook, USA

¹¹Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, USA

author email corresponding author email

BMC Endocrine Disorders 2007, 7:1doi:10.1186/1472-6823-7-1

Published:	30 March 2007

Abstract

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.