An uncoupling protein 3 gene polymorphism associated with a lower risk of developing Type II diabetes and with atherogenic lipid profile in a French cohort

Aims/hypothesis. The UCP2-UCP3 gene region has been previously associated w ith obesity and diabetes. In a large representative cohort of Northern Fran ce (MONICA project), we studied the effect of a recently reported CIT polym orphism located in the 5' sequences of the UCP3 gene on anthropometric meas urements and Lipid profile. We also examined the association of this polymo rphism with obesity and Type II (non-insulin-dependent) diabetes mellitus. Methods. The -55 C/T polymorphism of the UCP3 gene has been genotyped in 11 55 subjects from the MONICA project. Association studies were done with dia betes, obesity and related phenotypes. Results were ascertained in a second cohort of well-characterized Type II diabetic and control subjects. Results. The variant T allele was associated with a decreased risk of devel oping Type II diabetes. Frequencies of the T allele were 13.3 % compared wi th 22 %, p = 0.04, in the diabetic and control groups, respectively. This o bservation was confirmed in the second cohort of French Type II diabetic (n = 171) and control (n = 124) subjects: 17.8 % compared with 25 %, p = 0.03 . Moreover, subjects bearing the TT genotype had higher plasma total choles terol and LDL-cholesterol concentrations (p = 0.0006 and p = 0.001, respect ively) than subjects bearing wild or heterozygous genotypes. Conclusion/interpretation. The UCP3 -55 C/T polymorphism was associated wit h a higher atherogenic profile and modified the risk for the development of Type II diabetes.