UCP3 polymorphisms, hand grip performance and survival at old age: association analysis in two Danish middle aged and elderly cohorts.

An efficient uncoupling process is generally considered to have a protective effect on theaging muscle by slowing down its age-related decay. Genetic polymorphisms in the UncouplingProtein 3 (UCP3) gene, whose product is mainly expressed in skeletal muscle, were suggested to beassociated with hand grip performances in elderly populations. In our work, we aimed to add furthersupport to this evidence by analyzing the correlation between four SNPs in the UCP3 gene andrelative haplotypes, in two large cohorts of middle aged and oldest old Danes (N=1616). We foundthat the variability at two SNPs significantly influenced hand grip performance in both cohorts.Consistently, SNP combinations including significant alleles in single-locus analysis resulted indifferent haplotypic associations with hand grip performance. Finally, taking advantage of largecohort and period survival data of the oldest cohort, we tested the association of each SNP withsurvival at 10 years from the baseline visit. Interestingly, we found that alleles associated with handgrip scores showed differential survival patterns, with people carrying the allele negativelyinfluencing hand grip phenotype showing also higher mortality in our oldest cohort. On the whole,our work supports the role of UCP3 gene in functional status and survival at old age.