TY - JOUR
T1 - Nonsteroidal Anti-inflammatory Use and LRRK2 Parkinson's Disease Penetrance
AU - the Michael J. Fox Foundation LRRK2 Cohort Consortium
AU - San Luciano, Marta
AU - Tanner, Caroline M.
AU - Meng, Cheryl
AU - Marras, Connie
AU - Goldman, Samuel M.
AU - Lang, Anthony E.
AU - Tolosa, Eduardo
AU - Schüle, Birgitt
AU - Langston, J. William
AU - Brice, Alexis
AU - Corvol, Jean Christophe
AU - Goldwurm, Stefano
AU - Klein, Christine
AU - Brockman, Simone
AU - Berg, Daniela
AU - Brockmann, Kathrin
AU - Ferreira, Joachim J.
AU - Tazir, Meriem
AU - Mellick, George D.
AU - Sue, Carolyn M.
AU - Hasegawa, Kazuko
AU - Tan, Eng King
AU - Bressman, Susan
AU - Saunders-Pullman, Rachel
AU - Saunders-Pullman, Rachel
AU - Raymond, Deborah
AU - Deik, Andres
AU - Barrett, Matthew James
AU - Cabassa, Jose
AU - Groves, Mark
AU - Hunt, Ann L.
AU - Lubarr, Naomi
AU - Miravite, Joan
AU - Palmese, Christina
AU - Sachdev, Rivka
AU - Sarva, Harini
AU - Severt, Lawrence
AU - Shanker, Vicki
AU - Swan, Matthew Carrington
AU - Soto-Valencia, Jeannie
AU - Johannes, Brooke
AU - Ortega, Robert
AU - Ozelius, Laurie
AU - Bressman, Susan
AU - Alcalay, Roy N.
AU - Mirelman, Anat
AU - Gurevich, Tanya
AU - Thaler, Avner
AU - Orr-Urtreger, Avi
AU - Giladi, Nir
N1 - Publisher Copyright:
© 2020 International Parkinson and Movement Disorder Society
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85087894893&partnerID=8YFLogxK
U2 - 10.1002/mds.28189
DO - 10.1002/mds.28189
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C2 - 32662532
AN - SCOPUS:85087894893
SN - 0885-3185
VL - 35
SP - 1755
EP - 1764
JO - Movement Disorders
JF - Movement Disorders
IS - 10
ER -