阿司匹林对LRRK2-G2385R携带者帕金森病发病的前瞻性研究:来自于社区10年的随访研究

Relationship between aspirin and Parkinson's disease:A prospective longitudinal follow-up study in a community

中文关键词: LRRK2基因, 帕金森病, 阿斯匹林, 队列研究, 前瞻性研究, G2385R突变

英文关键词: elderly  LRRK2 gene  Parkinson's disease  aspirin  cohort study  prospective study  G2385R mutation

中文摘要:

      目的 探索阿斯匹林药物和帕金森病的关系,以及LRRK2基因在其中的作用.方法 本研究为基于社区的前瞻性研究,以2009-2011年来自于上海某社区正常老年人群的随访队列(≥60岁)为基础,通过问卷获取服用阿司匹林类药物的使用情况.在2020-2021年间,对这些人群进行了 LRRK2-G2385R的检测,并按照1∶1倾向性评分进行对照人群的匹配,建立了 LRRK2-G2385R易感位点(亚洲人群高发)的帕金森病高危人群队列,在2020-2021年间随访这个队列中新发帕金森病的情况,进行COX回归分析,并按照年龄(75岁)和基因(LRRK2-G2385R)进行分层分析.结果 共纳入267例LRRK2-G2385R携带者和276例对照者,新发帕金森病40例.在平衡干扰因素后,Cox回归分析发现阿司匹林对帕金森病的发病没有显著影响[(HR(95％CI))=1.979(0.949～4.126),P＞0.05].年龄分层后,在年龄≤75岁人群中阿司匹林显著增加了帕金森病发病的风险[HR(95％CI)=3.505(1.406～8.735),P=0.007],敏感性分析再次确认该阳性结果[HR(95％CI)=2.861(1.042～7.853),P=0.041].按照LRRK2-G2385R基因分层,也未发现阿司匹林对帕金森的发病影响.结论 利用随访10年人群的前瞻性研究设计,发现早期阿司匹林的使用与LRRK2-G2385R携带者的帕金森病发病并没有显著的相关性,但对于≤75岁的人群可能增加一定的患病风险.

英文摘要:

      Objective To investigate the relationship between aspirin and Parkinson's disease(PD),as well as the role of LRRK2 gene in it.Methods This study was a prospective community-based research.Based on a follow-up cohort of nor-mal elderly population(≥ 60 years old)from a community in Shanghai from 2009 to 2011,the use of aspirin drugs among them was obtained through a questionnaire.Between 2020 and 2021,the LRRK2-G2385R genotypes of this population were se-quenced.A control population was matched according to 1∶1 propensity score matching(PSM)method.A cohort of people at high risk for PD with the LRRK2-G2385R susceptibility locus(high prevalence in Asian populations)was established.This co-hort was followed up for new cases of PD in 2020-2021.COX regression analysis was performed,and stratified analysis was conducted based on age(75 years old)and gene(LRRK2-G2385R).Results A total of 267 LRRK2-G2385R carriers and 276 controls were included,including 40 new cases of PD.After balancing the confounding factors,Cox regression analysis found that aspirin had no significant effect on the onset of PD[(HR(95％CI)=1.979(0.949-4.126),P＞0.05].After stratified by age,it was found that aspirin significantly increased the risk of PD in the population aged ≤ 75 years[HR(95％CI)=3.505(1.406～8.735),P=0.007],and sensitivity analysis reconfirmed this positive result[HR(95％CI)=2.861(1.042～7.853),P=0.041].According to the LRRK2-G2385R gene stratification,no effect of aspirin on the onset of PD was found.Conclusion According to this prospective study results of the 10-year follow-up population,it is found that the early use of aspirin is not significantly correlated with the onset of PD in LRRK2-G2385R carriers,but it may increase the risk of the onset of PD in people ≤75 years.