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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Nonsteroidal Anti-inflammatory Use and LRRK2 Parkinson's Disease Penetrance
Movement Disorders, Volume 35, No. 10, Year 2020
Notification
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Description
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.
Authors & Co-Authors
San Luciano, Marta
United States, San Francisco
University of California, San Francisco
Tanner, Caroline M.
United States, San Francisco
University of California, San Francisco
United States, San Francisco
San Francisco va Health Care System
Meng, Cheryl
United States, San Francisco
University of California, San Francisco
Marras, Connie
Canada, Toronto
The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Centre
Canada, Toronto
Toronto Western Hospital University of Toronto
Goldman, Samuel M.
United States, San Francisco
University of California, San Francisco
United States, San Francisco
Ucsf School of Medicine
Lang, Anthony E.
Canada, Toronto
The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Centre
Canada, Toronto
Toronto Western Hospital University of Toronto
Tolosa, Eduardo S.
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas
Schüle, Birgitt
United States, Stanford
Stanford University School of Medicine
Langston, J. William
United States, Stanford
Stanford University School of Medicine
Brice, Alexis
France, Paris
Sorbonne Université
Corvol, Jean Christophe
France, Paris
Sorbonne Université
Goldwurm, S.
Italy, Milan
Istituti Clinici Di Perfezionamento
Klein, Christine
Germany, Lubeck
Universität zu Lübeck
Brockman, Simone
Australia, Perth
The University of Western Australia
Berg, Daniela
Germany, Tubingen
Hertie-institut Für Klinische Hirnforschung
Germany, Kiel
Christian-albrechts-universität zu Kiel
Brockmann, Kathrin
Germany, Tubingen
Hertie-institut Für Klinische Hirnforschung
Germany, Kiel
Christian-albrechts-universität zu Kiel
Ferreira, Joachim J.
Portugal, Lisbon
Instituto de Medicina Molecular
Tazir, Mériem
Algeria, Algiers
Centre Hospitalo-universitaire de Mustapha Bacha
Mellick, George D.
Australia, Brisbane
Griffith University
Sue, Carolyn M.
Australia, Sydney
Kolling Institute of Medical Research
Hasegawa, Kazuko
Japan, Sagamihara
National Hospital Organization Sagamihara National Hospital
Tan, Eng King
Singapore, Singapore City
Singapore General Hospital
Bressman, Susan B.
United States, New York
Icahn School of Medicine at Mount Sinai
Saunders-Pullman, Rachel J.
United States, New York
Icahn School of Medicine at Mount Sinai
Raymond, Deborah
Unknown Affiliation
Deik, Andres
Unknown Affiliation
Barrett, Matthew James
Unknown Affiliation
Cabassa, Jose
Unknown Affiliation
Groves, Mark
Unknown Affiliation
Hunt, Ann L.
Unknown Affiliation
Lubarr, Naomi
Unknown Affiliation
Miravite, Joan
Unknown Affiliation
Palmese, Christina
Unknown Affiliation
Sachdev, Rivka
Unknown Affiliation
Sarva, Harini
Unknown Affiliation
Severt, Lawrence
Unknown Affiliation
Shanker, Vicki
Unknown Affiliation
Swan, Matthew Carrington
Unknown Affiliation
Soto-Valencia, Jeannie
Unknown Affiliation
Johannes, Brooke
Unknown Affiliation
Ortega, Roberto A.
Unknown Affiliation
Ozelius, Laurie
Unknown Affiliation
Alcalay, Roy N.
Unknown Affiliation
Tang, Ming Xin
Unknown Affiliation
Santana, Helen Mejia
Unknown Affiliation
Roos, Ernest
Unknown Affiliation
Orbe-Reilly, Martha
Unknown Affiliation
Fahn, Stanley
Unknown Affiliation
Côté, Lucien J.
Unknown Affiliation
Waters, Cheryl H.
Unknown Affiliation
Mazzoni, Pietro
Unknown Affiliation
Ford, Blair
Unknown Affiliation
Louis, Elan Daniel
Unknown Affiliation
Levy, Oren
Unknown Affiliation
Rosado, Llency
Unknown Affiliation
Ruiz, Diana
Unknown Affiliation
Dorovski, Tsvyatko
Unknown Affiliation
Clark, Lorraine N.
Unknown Affiliation
Marder, Karen S.
Unknown Affiliation
Cormier, Florence
Unknown Affiliation
Bonnet, Anne Marie
Unknown Affiliation
Welter, Marie Laure
Unknown Affiliation
Mesnage, Valerie
Unknown Affiliation
Vidailhet, Marie
Unknown Affiliation
Roze, Emmanuel
Unknown Affiliation
Lacomblez, Lucette
Unknown Affiliation
Grabli, David
Unknown Affiliation
Mart i Masso, Jose Felix
Unknown Affiliation
Ruíz-Martínez, Javier
Unknown Affiliation
Mondragon Rezola, Elisabet
Unknown Affiliation
Alustiza, Ainara Estanga
Unknown Affiliation
Pagola, Ana Gorostidi
Unknown Affiliation
Pont-Sunyer, Claustre
Unknown Affiliation
Rolan, Dolores Vilas
Unknown Affiliation
Fernández-Santiago, Rubén
Unknown Affiliation
Quintana, Maria
Unknown Affiliation
Fernández-Martínez, Manuel Jesús
Unknown Affiliation
Maragall, Laura
Unknown Affiliation
Hentati, F. F.
Unknown Affiliation
Farrer, Matthew J.
Unknown Affiliation
Duda, John E.
Unknown Affiliation
Read, Matthew
Unknown Affiliation
Middleton, Lefkos T.
Unknown Affiliation
Gibson, Rachel A.
Unknown Affiliation
Trinh, Joanne
Unknown Affiliation
Ben Sassi, Samia
Unknown Affiliation
Zouari, Mourad
Unknown Affiliation
Rimamouri,
Unknown Affiliation
Farhat, Emna
Unknown Affiliation
Nabli, Fatma
Unknown Affiliation
Aasly, Jan Olav
Unknown Affiliation
Warø, Bjørg J.
Unknown Affiliation
Andersen, Sigrid
Unknown Affiliation
Bertoni, John M.
Unknown Affiliation
Carter, Julie H.
Unknown Affiliation
Elmer, Lawrence W.
Unknown Affiliation
Gálvez-Jiménez, Néstor A.
Unknown Affiliation
Statistics
Citations: 97
Authors: 97
Affiliations: 20
Identifiers
Doi:
10.1002/mds.28189
ISSN:
08853185
e-ISSN:
15318257
Research Areas
Genetics And Genomics
Study Design
Cohort Study
Case-Control Study