Catechol-O-Methyltransferase Genotype, Frailty, and Gait Speed in a Biracial Cohort of Older Adults.
Catechol-O-Methyltransferase Genotype, Frailty, and Gait Speed in a Biracial Cohort of Older Adults.
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DOI：
10.1111/jgs.16842
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发表时间：
2021-03
影响因子：
6.3
通讯作者：
Rosano C
中科院分区：
文献类型：
--
作者：
Mance S;Rosso A;Bis J;Studenski S;Bohnen N;Rosano C
检验多巴胺相关基因型与步速之间的关联是否因虚弱状态或种族而异。
基于人群的横断面研究（心血管健康研究）
多中心研究，美国4个地点。
65岁及以上的社区居住志愿者成年人，无帕金森病证据（N = 3744，71岁，82%为白人，39%为男性）。
评估了步速（正常步速，米/秒）、身体虚弱（弗里德定义）以及儿茶酚 - O - 甲基转移酶（COMT，rs4680）的基因多态性，该酶调节脑内多巴胺的紧张性水平。测试了COMT与虚弱以及与种族在预测步速方面的相互作用，如果显著，则进行分层分析。预测步速的COMT多变量回归模型根据人口统计学和运动危险因素进行了调整。敏感性分析按照步速的临床临界值（0.6米/秒和1.0米/秒）而非虚弱状态进行重复分层。
COMT与虚弱的相互作用以及COMT与种族的相互作用分别为p = 0.02和p = 0.01。与Met/Met（多巴胺能信号较高）相比，Val/Val组（多巴胺能信号较低）在整个队列中行走速度略慢（0.87米/秒对0.89米/秒，p = 0.2）。虚弱者（n = 220，0.55米/秒对0.63米/秒，p = 0.03）的步速差异显著，但虚弱前期（n = 1691，0.81米/秒对0.81米/秒，p = 0.9）或非虚弱者（n = 1833，0.98米/秒对0.97米/秒，p = 0.7）则不显著；在完全调整的模型中结果相似。在虚弱者中，白人和黑人的关联相似，但仅在白人中有统计学意义。按步速临床临界值分层的关联不显著。
与无虚弱的成年人相比，多巴胺相关基因型与步速的关联在虚弱成年人中更强。应进一步研究多巴胺能信号在不同种族的虚弱成年人中对维持身体功能的潜在影响。
To examine whether the association between dopamine-related genotype and gait speed differs according to frailty status or race. Cross-sectional population-based study (Cardiovascular Health Study) Multi-center study, 4 US sites. Volunteer community-dwelling adults aged 65 and older, without evidence of Parkinson’s Disease (N= 3,744, 71 years, 82% white, 39% male). Gait speed (usual pace, m/sec), physical frailty (Fried definition), and genetic polymorphism of Catechol-O-methyltransferase (COMT, rs4680), an enzyme regulating tonic brain dopamine levels, were assessed. Interaction of COMT by frailty and by race predicting gait speed were tested, and, if significant, analyses were stratified. Multivariable regression models of COMT predicting gait speed were adjusted for demographics and locomotor risk factors. Sensitivity analyses were repeated stratified by clinical cut-offs of gait speed (0.6 and 1.0m/sec) instead of frailty status. The interaction of COMT by frailty and COMT by race were p=0.02 and p=0.01, respectively. Compared to Met/Met (higher dopaminergic signaling), the Val/Val group (lower dopaminergic signaling) walked marginally more slowly in the full cohort (0.87 vs 0.89 m/sec, p=0.2). Gait speed differences were significant for frail (n=220, 0.55 vs 0.63 m/sec, p=0.03), but not for pre-frail (n=1691, 0.81 vs 0.81 m/sec, p=0.9), or non-frail (n=1833, 0.98 vs 0.97 m/sec, p=0.7); results were similar in fully adjusted models Among frail, associations were similar for whites and blacks, with statistical significance for whites only. Associations stratified by clinical cut-offs of gait speed were not significant. The association of dopamine-related genotype with gait speed is stronger among adults with frailty compared to those without. The potential effects of dopaminergic signaling on preserving physical function in biracial cohorts of frail adults should be further examined.
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影响因子：
5
作者：
PAFFENBARGER, RS;WING, AL;HYDE, RT
通讯作者：
HYDE, RT
影响因子：
8.2
作者：
Seidler, Rachael D.;Bernard, Jessica A.;Burutolu, Taritonye B.;Fling, Brett W.;Gordon, Mark T.;Gwin, Joseph T.;Kwak, Youngbin;Lipps, David B.
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
9.9
作者：
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通讯作者：
Rosano, Caterina
影响因子：
4.2
作者：
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通讯作者：
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