Nonsteroidal Anti‐inflammatory Use and LRRK2 Parkinson's Disease Penetrance. Issue 10 (14th July 2020)

• Record Type: Journal Article
• Authors: San Luciano, Marta; Tanner, Caroline M.; Meng, Cheryl; Marras, Connie; Goldman, Samuel M.; Lang, Anthony E.; Tolosa, Eduardo; Schüle, Birgitt; Langston, J. William; Brice, Alexis; Corvol, Jean‐Christophe; Goldwurm, Stefano; Klein, Christine; Brockman, Simone; Berg, Daniela; Brockmann, Kathrin; Ferreira, Joachim J.; Tazir, Meriem; Mellick, George D.; Sue, Carolyn M.; Hasegawa, Kazuko; Tan, Eng King; Bressman, Susan; Saunders‐Pullman, Rachel
• Other Names: Saunders‐Pullman Rachel investigator.; Raymond Deborah investigator.; Deik Andres investigator.; Barrett Matthew James investigator.; Cabassa Jose investigator.; Groves Mark investigator.; Hunt Ann L investigator.; Lubarr Naomi investigator.; Miravite Joan investigator.; Palmese Christina investigator.; Sachdev Rivka investigator.; Sarva Harini investigator.; Severt Lawrence investigator.; Shanker Vicki investigator.; Swan Matthew Carrington investigator.; Soto‐Valencia Jeannie investigator.; Johannes Brooke investigator.; Ortega Robert investigator.; Ozelius Laurie investigator.; Bressman Susan investigator.; Alcalay Roy N investigator.; Tang Ming‐X investigator.; Santana Helen Mejia investigator.; Roos Ernest investigator.; Orbe‐Reilly Martha investigator.; Fahn Stanley investigator.; Cote Lucien investigator.; Waters Cheryl investigator.; Mazzoni Pietro investigator.; Ford Blair investigator.; Louis Elan investigator.; Levy Oren investigator.; Rosado Llency investigator.; Ruiz Diana investigator.; Dorovski Tsvyatko investigator.; Clark Lorraine investigator.; Marder Karen S investigator.; Corvol Jean‐Christophe investigator.; Cormier Florence investigator.; Bonnet Anne‐Marie investigator.; Welter Marie‐Laure investigator.; Mesnage Valerie investigator.; Vidailhet Marie investigator.; Roze Emmanuel investigator.; Lacomblez Lucette investigator.; Grabli David investigator.; Mart i Masso Jose Felix investigator.; Martinez Javier Ruiz investigator.; Mondragon Rezola Elisabet investigator.; Alustiza Ainara Estanga investigator.; Pagola Ana Gorostidi investigator.; Pont‐Sunyer Claustre investigator.; Rolan Dolores Vilas investigator.; Fernandez‐Santiago Ruben investigator.; Quintana Maria investigator.; Fernandez Manel investigator.; Maragall Laura investigator.; Hentati Faycal investigator.; Farrer Matthew investigator.; Duda John investigator.; Read Matt investigator.; Middleton Lefkos investigator.; Gibson Rachel investigator.; Trinh Joanne investigator.; Sassi Samia Ben investigator.; Zouari Mourad investigator.; Rimamouri investigator.; Farhat Emna investigator.; Nabli Fatma investigator.; Aasly Jan investigator.; Warø Bjørg Johanne investigator.; Andersen Sigrid investigator.; Bertoni John investigator.; Carter Julie investigator.; Elmer Lawrence investigator.; Jimenez Nestor Galvez investigator.; Martin Wayne investigator.; Pahwa Rajesh investigator.; Lyons Kelly investigator.; Reich Stephen investigator.; Rodnitzky Robert investigator.; Ramos Carmen Serrano investigator.; Wojcieszek Joanne investigator.; Mirelman Anat investigator.; Gurevich Tanya investigator.; Shira Anat Bar investigator.; Weisz Mali Gana investigator.; Yasinovsky Kira investigator.; Zalis Maayan investigator.; Thaler Avner investigator.; Orr‐Urtreger Avi investigator.; Giladi Nir investigator.; Mountain Joanna investigator.; Mestre Tiago investigator.; Visanji Naomi investigator.; Ghate Taneera investigator.; Singerman Jennifer investigator.; Al Dakheel Amaal investigator.; Connolly Barbara S investigator.; Gasser Thomas investigator.; Brockmann Kathrin investigator.; Conley Emily Drabant investigator.; Mullins Meghan E investigator.; Northover Carrie investigator.; Facheris Maurizio investigator.; Fiske Brian investigator.; Urkowiz Alison investigator.;
• Is Part Of: Movement disorders. Volume 35:Issue 10(2020)
• Page Start: 1755
• Page End: 1764
• Publication Date: 2020-07-14
• Subjects: Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.28189
• Languages: English
• ISSNs: 0885-3185

Abstract

Abstract: Background: The penetrance of leucine rich repeat kinase 2 ( LRRK2 ) mutations is incomplete and may be influenced by environmental and/or other genetic factors. Nonsteroidal 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. Objectives: The objective of this study is to evaluate the association of regular NSAID use and LRRK2 ‐associated PD. Methods: Symptomatic ("LRRK2‐PD") and asymptomatic ("LRRK2‐non‐PD") participants with LRRK2 G2019S, R1441X, or I2020T variants (definitely pathogenic variant carriers) or G2385R or R1628P variants (risk variant carriers) from 2 international cohorts provided information on regular ibuprofen and/or aspirin use (≥2 pills/week for ≥6 months) prior to the 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. Results: A total of 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 (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.21–0.57) and in both pathogenic and risk variant carriers (ORPathogenic, 0.38; 95% CI, 0.21–0.67 and 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 and ORAspirin, 0.51; 95% CI, 0.28–0.91). Conclusions: 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. © 2020 International Parkinson and Movement Disorder Society