03126nas a2200373 4500008004100000022001400041245008700055210006900142260001600211300001100227490000600238520210800244653000902352653002202361653002302383653001102406653001802417653001302435653001102448653000902459653002602468100001802494700001902512700001802531700002102549700001902570700002102589700002102610700002002631700002002651700002602671700001902697856003602716 2010 eng d a1932-620300aPolymorphisms in the mitochondrial DNA control region and frailty in older adults.0 aPolymorphisms in the mitochondrial DNA control region and frailt c2010 Jun 10 ae110690 v53 a

BACKGROUND: Mitochondria contribute to the dynamics of cellular metabolism, the production of reactive oxygen species, and apoptotic pathways. Consequently, mitochondrial function has been hypothesized to influence functional decline and vulnerability to disease in later life. Mitochondrial genetic variation may contribute to altered susceptibility to the frailty syndrome in older adults.

METHODOLOGY/PRINCIPAL FINDINGS: To assess potential mitochondrial genetic contributions to the likelihood of frailty, mitochondrial DNA (mtDNA) variation was compared in frail and non-frail older adults. Associations of selected SNPs with a muscle strength phenotype were also explored. Participants were selected from the Cardiovascular Health Study (CHS), a population-based observational study (1989-1990, 1992-1993). At baseline, frailty was identified as the presence of three or more of five indicators (weakness, slowness, shrinking, low physical activity, and exhaustion). mtDNA variation was assessed in a pilot study, including 315 individuals selected as extremes of the frailty phenotype, using an oligonucleotide sequencing microarray based on the Revised Cambridge Reference Sequence. Three mtDNA SNPs were statistically significantly associated with frailty across all pilot participants or in sex-stratified comparisons: mt146, mt204, and mt228. In addition to pilot participants, 4,459 additional men and women with frailty classifications, and an overlapping subset of 4,453 individuals with grip strength measurements, were included in the study population genotyped at mt204 and mt228. In the study population, the mt204 C allele was associated with greater likelihood of frailty (adjusted odds ratio = 2.04, 95% CI = 1.07-3.60, p = 0.020) and lower grip strength (adjusted coefficient = -2.04, 95% CI = -3.33- -0.74, p = 0.002).

CONCLUSIONS: This study supports a role for mitochondrial genetic variation in the frailty syndrome and later life muscle strength, demonstrating the importance of the mitochondrial genome in complex geriatric phenotypes.

10aAged10aAged, 80 and over10aDNA, Mitochondrial10aFemale10aFrail Elderly10aGenotype10aHumans10aMale10aPolymorphism, Genetic1 aMoore, Ann, Z1 aBiggs, Mary, L1 aMatteini, Amy1 aO'Connor, Ashley1 aMcGuire, Sarah1 aBeamer, Brock, A1 aFallin, Danielle1 aFried, Linda, P1 aWalston, Jeremy1 aChakravarti, Aravinda1 aArking, Dan, E uhttps://chs-nhlbi.org/node/1205