We explored the associations of three variants in the uncoupling protein 2 (UCP2) gene, one variant in the UCP2-UCP3 intergenic region and five variants in the uncoupling protein 3 (UCP3) gene with obesity and diabetes related traits in subjects with impaired glucose tolerance participating in Finnish Diabetes Prevention Study.
The genotype (P = 0.02) and the allele (P = 0.002) frequencies of -55C/T of the UCP3 gene showed a significant protective effect against the development of diabetes.
These findings suggest a role of UCP2-UCP3 gene cluster haplotypes in diabetes; in particular, the effects of the high-risk haplotypes were more apparent in overweight Caucasian women.
To test this hypothesis we searched for association between the A-->G (-3862) variant in UCP1, the insertion/deletion (I/D) polymorphism in exon 8 in UCP2, and the C-->T (-55) polymorphism in UCP3 and diabetic nephropathy in 218 diabetic patients with normal urinary albumin excretion rate (AER), 216 with micro- or macroalbuminuria, and in 106 control subjects without a family history of diabetes.
This review summarizes data supporting the roles of UCP2 and UCP3 in energy dissipation, as well as the genetic variety association with fat metabolism, obesity and diabetes in humans.
The presence of a mixed genetic background in most published studies of UCP2 or UCP3 gene-ablated mice also means that data concerning marked differences in diabetes propensity, infection sensitivity and production of reactive oxygen species may require confirmation in backcrossed mice.