Nonsteroidal Anti-inflammatory Use and LRRK2 Parkinson's Disease Penetrance.
Nonsteroidal Anti-inflammatory Use and LRRK2 Parkinson's Disease Penetrance.
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DOI：
10.1002/mds.28189
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发表时间：
2020-10
期刊：
影响因子：
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通讯作者：
Michael J. Fox Foundation LRRK2 Cohort Consortium
中科院分区：
文献类型：
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作者：
San Luciano M;Tanner CM;Meng C;Marras C;Goldman SM;Lang AE;Tolosa E;Schüle B;Langston JW;Brice A;Corvol JC;Goldwurm S;Klein C;Brockman S;Berg D;Brockmann K;Ferreira JJ;Tazir M;Mellick GD;Sue CM;Hasegawa K;Tan EK;Bressman S;Saunders-Pullman R;Michael J. Fox Foundation LRRK2 Cohort Consortium
富含亮氨酸重复激酶2（LRRK 2）突变的遗传不完全，可能受环境和/或其他遗传因素的影响。已知非甾体抗炎药（NSAID）可减少炎症，并可降低帕金森病（PD）风险，但其在LRRK 2相关PD中的作用尚不清楚。评价定期使用NSAID与LRRK 2相关PD的相关性。症状性（“LRRK 2-PD”）和无症状（“LRRK 2-nonPD”）具有LRRK 2 G2019 S、R1441 X或I2020 T变体的受试者（“明确致病性变异携带者”），或G2385 R或R1628 P变体（“风险变异携带者”）提供了关于布洛芬和/或阿司匹林常规使用的信息（≥2片/周，持续≥6个月）。多变量逻辑回归用于评估任何NSAID的常规NSAID使用与PD之间的关系，在所有携带者中分别为布洛芬和阿司匹林，并分别在致病性和风险变异组中。入组了259例LRRK 2-PD和318例LRRK 2-非PD受试者。在整个队列（OR=0.34，95%CI 0.21-0.57）以及致病性和风险变异携带者（ORPathogenic=0.38，95%CI 0.21-0.67; ORRiskVariant=0.19，95%CI 0.04-0.99）中，定期使用NSAID与PD几率降低相关。布洛芬和阿司匹林分别观察到类似的相关性（ORIBIVE =0.19，95%CI 0.07-0.50，ORAspirin=0.51，95%CI 0.28-0.91）。定期使用NSAID可能与LRRK 2相关PD的发病率降低相关。LRRK 2蛋白参与炎症途径，似乎可以通过定期使用抗炎药物进行调节。需要对NSAID暴露和LRRK 2-PD进行纵向观察性和干预性研究以证实这种关联。
The penetrance of Leucine Rich Repeat Kinase 2 (LRRK2) mutations is incomplete and may be influenced by environmental and/or other genetic factors. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to reduce inflammation and may lower Parkinson’s disease (PD) risk, but their role in LRRK2-associated PD is unknown. To evaluate the association of regular NSAID use and LRRK2 associated PD. Symptomatic (“LRRK2-PD”) and asymptomatic (“LRRK2-nonPD”) participants with LRRK2 G2019S, R1441X or I2020T variants (“definitely pathogenic variant carriers”), or G2385R or R1628P variants (“risk variant carriers”) from two international cohorts provided information on regular ibuprofen and/or aspirin use (≥2 pills/week for ≥6 months) prior to index date (diagnosis date for PD, interview date for non-PD). Multivariate logistic regression was used to evaluate the relationship between regular NSAID use and PD for any NSAID, separately for ibuprofen and aspirin in all carriers and separately in pathogenic and risk variant groups. 259 LRRK2-PD and 318 LRRK2-non-PD participants were enrolled. Regular NSAID use was associated with reduced odds of PD in the overall cohort (OR=0.34, 95%CI 0.21–0.57), and in both pathogenic and risk variant carriers (ORPathogenic=0.38, 95%CI 0.21–0.67; ORRiskVariant=0.19, 95%CI 0.04–0.99). Similar associations were observed for ibuprofen and aspirin separately (ORIbuprofen=0.19, 95%CI 0.07–0.50, ORAspirin=0.51, 95%CI 0.28–0.91). Regular NSAID use may be associated with reduced penetrance in LRRK2-associated PD. The LRRK2 protein is involved in inflammatory pathways and appears to be modulated by regular anti-inflammatory use. Longitudinal observational and interventional studies of NSAID exposure and LRRK2-PD are needed to confirm this association.