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 the aging muscle by slowing down its age-related decay. Genetic polymorphisms in the Uncoupling Protein 3 (UCP3) gene, whose product is mainly expressed in skeletal muscle, were suggested to be associated with hand grip (HG) performances in elderly populations. Considering the population specificity of the quality of aging, we aimed to add further support to this evidence by analyzing the association between four SNPs in the UCP3 gene and relative haplotypes in two large cohorts of middle aged (N = 708) and oldest old Danes (N = 908). We found that the variability at rs1685354 and rs11235972 was associated with HG levels both at single and haplotypic level in both cohorts. Furthermore, taking advantage of large cohort and period survival data of the oldest cohort, we tested the association of each SNP with survival at 10 years from the baseline visit. Interestingly, we found that allele A at rs11235972, associated in this cohort with lowest HG scores, influences also the survival patterns, with people carrying this allele showing higher mortality rates. On the whole, our work supports the role of UCP3 gene in functional status and survival at old age.

► Efficient uncoupling process has a protective effect on the aging muscle by slowing down its age-related decay.
► Hand grip strength is a reliable marker of the functional status and a predictor of disability/mortality in the elderly.
► We analyzed the association between four SNPs at uncoupling protein 3 gene (UCP3) and hand grip in 1616 middle aged and oldest old Danes.
► Association with hand grip levels was found for rs1685354 and rs11235972 in the oldest old, the second influencing also the survival at old age.