Metti Andrea L, Rosano Caterina, Boudreau Robert, Massa Robyn, Yaffe Kristine, Satterfield Suzanne, Harris Tamara, Rosso Andrea L
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania.
J Am Geriatr Soc. 2017 Sep;65(9):2016-2022. doi: 10.1111/jgs.14980. Epub 2017 Jun 22.
To determine the association between catechol-O-methyltransferase (COMT) genotype and 6-m walk time and to determine whether these associations are quadratic in nature, similar to previously reported U-shaped associations between dopamine and gait and cognition.
Prospective cohort study.
Health, Aging and Body Composition Study.
Black (n = 850) and white (n = 1,352) men and women with a mean age of 73.5 ± 2.85 at baseline.
Mixed models were used to assess the association between the COMT genotype and 6-m walk time, cross-sectionally and longitudinally over 10 years. Models were assessed unstratified and stratified according to race because allele distributions were different between white and black participants.
There was a significant U-shaped association between COMT genotype and 6-m walk time: those with higher (Val/Val) and lower (Met/Met) dopamine slowed more over 10 years (0.22 ± 0.02 seconds per visit and 0.23 ± 0.02 seconds per visit, respectively) than those with the intermediate (Met/Val) dopamine (0.20 ± 0.02 seconds per visit) (P = .005). Stratified results showed a significant relationship in black (P = .01) but not white (P = .15) participants.
These findings indicate a role of dopaminergic regulation of gait speed in community-dwelling older adults and of prefrontal cortex involvement in gait performance. Future work should investigate the molecular integrity of dopaminergic networks and gait changes over time and structural changes in the brain with COMT and gait decline in older adults.
确定儿茶酚-O-甲基转移酶（COMT）基因型与6分钟步行时间之间的关联，并确定这些关联是否呈二次曲线性质，类似于先前报道的多巴胺与步态和认知之间的U型关联。
前瞻性队列研究。
健康、衰老和身体成分研究。
基线时平均年龄为73.5±2.85岁的黑人（n = 850）和白人（n = 1352）男性和女性。
使用混合模型在横断面和10年纵向研究中评估COMT基因型与6分钟步行时间之间的关联。根据种族对模型进行未分层和分层评估，因为白人和黑人参与者的等位基因分布不同。
COMT基因型与6分钟步行时间之间存在显著的U型关联：多巴胺水平较高（Val/Val）和较低（Met/Met）的人在10年中步行速度减慢更多（分别为每次随访0.22±0.02秒和0.23±0.02秒），高于多巴胺水平中等（Met/Val）的人（每次随访0.20±0.02秒）（P = 0.005）。分层结果显示，黑人参与者中有显著关系（P = 0.01），而白人参与者中无显著关系（P = 0.15）。
这些发现表明多巴胺能对社区居住的老年人步态速度的调节作用以及前额叶皮层参与步态表现。未来的工作应研究多巴胺能网络的分子完整性以及随着时间推移的步态变化，以及老年人中COMT与步态衰退相关的大脑结构变化。
