Nonsteroidal Anti-inflammatory Use and LRRK2 Parkinson's Disease Penetrance.
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
17
03
2020
revised:
15
05
2020
accepted:
08
06
2020
pubmed:
15
7
2020
medline:
28
4
2021
entrez:
15
7
2020
Statut:
ppublish
Résumé
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. The objective of this study is to evaluate the association of regular NSAID use and LRRK2-associated PD. 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. 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 (OR 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.
Sections du résumé
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 (OR
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.
Identifiants
pubmed: 32662532
doi: 10.1002/mds.28189
pmc: PMC7572560
mid: NIHMS1611810
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
LRRK2 protein, human
EC 2.7.11.1
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1755-1764Subventions
Organisme : NINDS NIH HHS
ID : K23 NS099441
Pays : United States
Investigateurs
Rachel Saunders-Pullman
(R)
Deborah Raymond
(D)
Andres Deik
(A)
Matthew James Barrett
(MJ)
Jose Cabassa
(J)
Mark Groves
(M)
Ann L Hunt
(AL)
Naomi Lubarr
(N)
Joan Miravite
(J)
Christina Palmese
(C)
Rivka Sachdev
(R)
Harini Sarva
(H)
Lawrence Severt
(L)
Vicki Shanker
(V)
Matthew Carrington Swan
(MC)
Jeannie Soto-Valencia
(J)
Brooke Johannes
(B)
Robert Ortega
(R)
Laurie Ozelius
(L)
Susan Bressman
(S)
Roy N Alcalay
(RN)
Ming-X Tang
(MX)
Helen Mejia Santana
(HM)
Ernest Roos
(E)
Martha Orbe-Reilly
(M)
Stanley Fahn
(S)
Lucien Cote
(L)
Cheryl Waters
(C)
Pietro Mazzoni
(P)
Blair Ford
(B)
Elan Louis
(E)
Oren Levy
(O)
Llency Rosado
(L)
Diana Ruiz
(D)
Tsvyatko Dorovski
(T)
Lorraine Clark
(L)
Karen S Marder
(KS)
Jean-Christophe Corvol
(JC)
Florence Cormier
(F)
Anne-Marie Bonnet
(AM)
Marie-Laure Welter
(ML)
Valerie Mesnage
(V)
Marie Vidailhet
(M)
Emmanuel Roze
(E)
Lucette Lacomblez
(L)
David Grabli
(D)
Jose Felix Mart I Masso
(JF)
Javier Ruiz Martinez
(JR)
Elisabet Mondragon Rezola
(E)
Ainara Estanga Alustiza
(AE)
Ana Gorostidi Pagola
(AG)
Claustre Pont-Sunyer
(C)
Dolores Vilas Rolan
(DV)
Ruben Fernandez-Santiago
(R)
Maria Quintana
(M)
Manel Fernandez
(M)
Laura Maragall
(L)
Faycal Hentati
(F)
Matthew Farrer
(M)
John Duda
(J)
Matt Read
(M)
Lefkos Middleton
(L)
Rachel Gibson
(R)
Joanne Trinh
(J)
Samia Ben Sassi
(SB)
Mourad Zouari
(M)
None Rimamouri
Emna Farhat
(E)
Fatma Nabli
(F)
Jan Aasly
(J)
Bjørg Johanne Warø
(BJ)
Sigrid Andersen
(S)
John Bertoni
(J)
Julie Carter
(J)
Lawrence Elmer
(L)
Nestor Galvez Jimenez
(NG)
Wayne Martin
(W)
Rajesh Pahwa
(R)
Kelly Lyons
(K)
Stephen Reich
(S)
Robert Rodnitzky
(R)
Carmen Serrano Ramos
(CS)
Joanne Wojcieszek
(J)
Anat Mirelman
(A)
Tanya Gurevich
(T)
Anat Bar Shira
(AB)
Mali Gana Weisz
(MG)
Kira Yasinovsky
(K)
Maayan Zalis
(M)
Avner Thaler
(A)
Avi Orr-Urtreger
(A)
Nir Giladi
(N)
Joanna Mountain
(J)
Tiago Mestre
(T)
Naomi Visanji
(N)
Taneera Ghate
(T)
Jennifer Singerman
(J)
Amaal Al Dakheel
(A)
Barbara S Connolly
(BS)
Thomas Gasser
(T)
Kathrin Brockmann
(K)
Emily Drabant Conley
(ED)
Meghan E Mullins
(ME)
Carrie Northover
(C)
Maurizio Facheris
(M)
Brian Fiske
(B)
Alison Urkowiz
(A)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2020 International Parkinson and Movement Disorder Society.
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