Polymorphisms in the mitochondrial DNA control region and frailty in older adults.
Polymorphisms in the mitochondrial DNA control region and frailty in older adults.
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DOI：
10.1371/journal.pone.0011069
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发表时间：
2010-06-10
期刊：
影响因子：
3.7
通讯作者：
Arking DE
中科院分区：
文献类型：
--
作者：
Moore AZ;Biggs ML;Matteini A;O'Connor A;McGuire S;Beamer BA;Fallin MD;Fried LP;Walston J;Chakravarti A;Arking DE
线粒体有助于细胞代谢的动态、活性氧的产生和细胞凋亡途径。因此，假设线粒体功能会影响晚年的功能衰退和疾病易感性。线粒体遗传变异可能导致老年人对衰弱综合征的易感性改变。为了评估线粒体遗传对衰弱可能性的潜在影响，对衰弱和非衰弱老年人的线粒体 DNA (mtDNA) 变异进行了比较。还探讨了选定的 SNP 与肌肉力量表型的关联。参与者选自心血管健康研究（CHS），这是一项基于人群的观察性研究（1989-1990、1992-1993）。在基线时，虚弱被确定为存在五个指标中的三个或更多（虚弱、缓慢、萎缩、体力活动少和疲惫）。在一项试点研究中评估了 mtDNA 变异，其中包括 315 名被选为脆弱表型极端的个体，使用基于修订的剑桥参考序列的寡核苷酸测序微阵列。三个 mtDNA SNP 在所有试点参与者中或在性别分层比较中与虚弱具有统计显着相关性：mt146、mt204 和 mt228。除了试点参与者之外，在 mt204 和 mt228 进行基因分型的研究人群中还包括 4,459 名具有衰弱分类的男性和女性，以及 4,453 名具有握力测量值的重叠子集。在研究人群中，mt204 C 等位基因与更大的虚弱可能性相关（调整后的比值比 = 2.04，95% CI = 1.07–3.60，p = 0.020）和较低的握力（调整后的系数 = −2.04，95% CI = −3.33– −0.74, p = 0.002)。这项研究支持线粒体遗传变异在衰弱综合征和晚年肌肉力量中的作用，证明了线粒体基因组在复杂的老年表型中的重要性。
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. 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). 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.
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DOI：
10.1093/gerona/61.3.262
发表时间：
2006-03-01
影响因子：
5.1
作者：
Bandeen-Roche, K;Xue, QL;Fried, LP
通讯作者：
Fried, LP
影响因子：
56.9
作者：
Wilson, FH;Hariri, A;Lifton, RP
通讯作者：
Lifton, RP
影响因子：
9.8
作者：
van der Walt, JM;Nicodemus, KK;Vance, JM
通讯作者：
Vance, JM
影响因子：
9.8
作者：
Fischel-Ghodsian, N
通讯作者：
Fischel-Ghodsian, N
影响因子：
3.5
作者：
Poulton, J;Luan, J;Wareham, NJ
通讯作者：
Wareham, NJ