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.
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).


CONCLUSIONS
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.
Sale
Michèle M
MM
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, USA. msale@virginia.edu
Hsu
Fang-Chi
FC
Palmer
Nicholette D
ND
Gordon
Candace J
CJ
Keene
Keith L
KL
Borgerink
Hermina M
HM
Sharma
Arun J
AJ
Bergman
Richard N
RN
Taylor
Kent D
KD
Saad
Mohammed F
MF
Norris
Jill M
JM