Nonsteroidal Anti‐inflammatory Use and LRRK2 Parkinson's Disease Penetrance
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 ro...
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| Veröffentlicht in: | Movement disorders 2020-10, Vol.35 (10), p.1755-1764 |
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| creator | San Luciano, Marta Tanner, Caroline M. Meng, Cheryl Marras, Connie Lang, Anthony E. Schüle, Birgitt Langston, J. William Corvol, Jean‐Christophe Goldwurm, Stefano Berg, Daniela Tazir, Meriem Mellick, George D. Sue, Carolyn M. Tan, Eng King Bressman, Susan Saunders‐Pullman, Rachel Raymond, Deborah Barrett, Matthew James Cabassa, Jose Groves, Mark Hunt, Ann L Lubarr, Naomi Palmese, Christina Sachdev, Rivka Sarva, Harini Shanker, Vicki Swan, Matthew Carrington Soto‐Valencia, Jeannie Johannes, Brooke Ortega, Robert Alcalay, Roy N Tang, Ming‐X Santana, Helen Mejia Orbe‐Reilly, Martha Fahn, Stanley Cote, Lucien Ford, Blair Louis, Elan Levy, Oren Rosado, Llency Ruiz, Diana Clark, Lorraine Marder, Karen S Corvol, Jean‐Christophe Bonnet, Anne‐Marie Welter, Marie‐Laure Mesnage, Valerie Vidailhet, Marie Roze, Emmanuel Lacomblez, Lucette Grabli, David Mart i Masso, Jose Felix Mondragon Rezola, Elisabet Alustiza, Ainara Estanga Pagola, Ana Gorostidi Pont‐Sunyer, Claustre Rolan, Dolores Vilas Fernandez‐Santiago, Ruben Quintana, Maria Maragall, Laura Hentati, Faycal Farrer, Matthew Duda, John Read, Matt Gibson, Rachel Sassi, Samia Ben Zouari, Mourad Nabli, Fatma Aasly, Jan Andersen, Sigrid Bertoni, John Carter, Julie Elmer, Lawrence Jimenez, Nestor Galvez Martin, Wayne Pahwa, Rajesh Lyons, Kelly Reich, Stephen Ramos, Carmen Serrano Wojcieszek, Joanne Gurevich, Tanya Shira, Anat Bar Weisz, Mali Gana Yasinovsky, Kira Zalis, Maayan Thaler, Avner Orr‐Urtreger, Avi Giladi, Nir Mountain, Joanna Mestre, Tiago Ghate, Taneera Singerman, Jennifer Al Dakheel, Amaal Connolly, Barbara S Gasser, Thomas Brockmann, Kathrin Mullins, Meghan E Northover, Carrie Facheris, Maurizio Fiske, Brian |
| 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 |
| doi_str_mv | 10.1002/mds.28189 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_04574532v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2451546877</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4229-83ba761ccb71764f8e065326a313b0c96390f7ce150fc9ee648bf9ac0a68bb63</originalsourceid><addsrcrecordid>eNp1kMtOwkAUQCdGI4gu_AHTxIVxUZhHZzpdElAxFiWI68l0mMZiO8WZomHnJ_iNfonFIq5c3eTek5ObA8Apgl0EIe4Vc9fFHPFoD7QRJcjnmIb7oA05pz5BnLbAkXMLCBGiiB2CFsGMYUpwG4zvS-MqbctsLnOvb6rs6-MzM2kui0JWpV17T0570sy9eDq9w95E2pfMuNJcOG-YOS3r60QbXVlplD4GB6nMnT7Zzg6YXV_NBiM_fri5HfRjXwUYRz4niQwZUioJUciClGvI6m-YJIgkUEWMRDANlUYUpirSmgU8SSOpoGQ8SRjpgMtG-yxzsbRZIe1alDITo34sNjsY0DCojW-oZs8bdmnL15V2lViUK2vq7wQOKKIB42H4Z1S2dM7qdKdFUGwai7qx-Glcs2db4yop9HxH_katgV4DvGe5Xv9vEuPhY6P8BhtHhLY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2451546877</pqid></control><display><type>article</type><title>Nonsteroidal Anti‐inflammatory Use and LRRK2 Parkinson's Disease Penetrance</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>San Luciano, Marta ; Tanner, Caroline M. ; Meng, Cheryl ; Marras, Connie ; Lang, Anthony E. ; Schüle, Birgitt ; Langston, J. William ; Corvol, Jean‐Christophe ; Goldwurm, Stefano ; Berg, Daniela ; Tazir, Meriem ; Mellick, George D. ; Sue, Carolyn M. ; Tan, Eng King ; Bressman, Susan ; Saunders‐Pullman, Rachel ; Raymond, Deborah ; Barrett, Matthew James ; Cabassa, Jose ; Groves, Mark ; Hunt, Ann L ; Lubarr, Naomi ; Palmese, Christina ; Sachdev, Rivka ; Sarva, Harini ; Shanker, Vicki ; Swan, Matthew Carrington ; Soto‐Valencia, Jeannie ; Johannes, Brooke ; Ortega, Robert ; Alcalay, Roy N ; Tang, Ming‐X ; Santana, Helen Mejia ; Orbe‐Reilly, Martha ; Fahn, Stanley ; Cote, Lucien ; Ford, Blair ; Louis, Elan ; Levy, Oren ; Rosado, Llency ; Ruiz, Diana ; Clark, Lorraine ; Marder, Karen S ; Corvol, Jean‐Christophe ; Bonnet, Anne‐Marie ; Welter, Marie‐Laure ; Mesnage, Valerie ; Vidailhet, Marie ; Roze, Emmanuel ; Lacomblez, Lucette ; Grabli, David ; Mart i Masso, Jose Felix ; Mondragon Rezola, Elisabet ; Alustiza, Ainara Estanga ; Pagola, Ana Gorostidi ; Pont‐Sunyer, Claustre ; Rolan, Dolores Vilas ; Fernandez‐Santiago, Ruben ; Quintana, Maria ; Maragall, Laura ; Hentati, Faycal ; Farrer, Matthew ; Duda, John ; Read, Matt ; Gibson, Rachel ; Sassi, Samia Ben ; Zouari, Mourad ; Nabli, Fatma ; Aasly, Jan ; Andersen, Sigrid ; Bertoni, John ; Carter, Julie ; Elmer, Lawrence ; Jimenez, Nestor Galvez ; Martin, Wayne ; Pahwa, Rajesh ; Lyons, Kelly ; Reich, Stephen ; Ramos, Carmen Serrano ; Wojcieszek, Joanne ; Gurevich, Tanya ; Shira, Anat Bar ; Weisz, Mali Gana ; Yasinovsky, Kira ; Zalis, Maayan ; Thaler, Avner ; Orr‐Urtreger, Avi ; Giladi, Nir ; Mountain, Joanna ; Mestre, Tiago ; Ghate, Taneera ; Singerman, Jennifer ; Al Dakheel, Amaal ; Connolly, Barbara S ; Gasser, Thomas ; Brockmann, Kathrin ; Mullins, Meghan E ; Northover, Carrie ; Facheris, Maurizio ; Fiske, Brian</creator><creatorcontrib>San Luciano, Marta ; Tanner, Caroline M. ; Meng, Cheryl ; Marras, Connie ; Lang, Anthony E. ; Schüle, Birgitt ; Langston, J. William ; Corvol, Jean‐Christophe ; Goldwurm, Stefano ; Berg, Daniela ; Tazir, Meriem ; Mellick, George D. ; Sue, Carolyn M. ; Tan, Eng King ; Bressman, Susan ; Saunders‐Pullman, Rachel ; Raymond, Deborah ; Barrett, Matthew James ; Cabassa, Jose ; Groves, Mark ; Hunt, Ann L ; Lubarr, Naomi ; Palmese, Christina ; Sachdev, Rivka ; Sarva, Harini ; Shanker, Vicki ; Swan, Matthew Carrington ; Soto‐Valencia, Jeannie ; Johannes, Brooke ; Ortega, Robert ; Alcalay, Roy N ; Tang, Ming‐X ; Santana, Helen Mejia ; Orbe‐Reilly, Martha ; Fahn, Stanley ; Cote, Lucien ; Ford, Blair ; Louis, Elan ; Levy, Oren ; Rosado, Llency ; Ruiz, Diana ; Clark, Lorraine ; Marder, Karen S ; Corvol, Jean‐Christophe ; Bonnet, Anne‐Marie ; Welter, Marie‐Laure ; Mesnage, Valerie ; Vidailhet, Marie ; Roze, Emmanuel ; Lacomblez, Lucette ; Grabli, David ; Mart i Masso, Jose Felix ; Mondragon Rezola, Elisabet ; Alustiza, Ainara Estanga ; Pagola, Ana Gorostidi ; Pont‐Sunyer, Claustre ; Rolan, Dolores Vilas ; Fernandez‐Santiago, Ruben ; Quintana, Maria ; Maragall, Laura ; Hentati, Faycal ; Farrer, Matthew ; Duda, John ; Read, Matt ; Gibson, Rachel ; Sassi, Samia Ben ; Zouari, Mourad ; Nabli, Fatma ; Aasly, Jan ; Andersen, Sigrid ; Bertoni, John ; Carter, Julie ; Elmer, Lawrence ; Jimenez, Nestor Galvez ; Martin, Wayne ; Pahwa, Rajesh ; Lyons, Kelly ; Reich, Stephen ; Ramos, Carmen Serrano ; Wojcieszek, Joanne ; Gurevich, Tanya ; Shira, Anat Bar ; Weisz, Mali Gana ; Yasinovsky, Kira ; Zalis, Maayan ; Thaler, Avner ; Orr‐Urtreger, Avi ; Giladi, Nir ; Mountain, Joanna ; Mestre, Tiago ; Ghate, Taneera ; Singerman, Jennifer ; Al Dakheel, Amaal ; Connolly, Barbara S ; Gasser, Thomas ; Brockmann, Kathrin ; Mullins, Meghan E ; Northover, Carrie ; Facheris, Maurizio ; Fiske, Brian ; Michael J. Fox Foundation LRRK2 Cohort Consortium ; the Michael J. Fox Foundation LRRK2 Cohort Consortium</creatorcontrib><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</description><identifier>ISSN: 0885-3185</identifier><identifier>EISSN: 1531-8257</identifier><identifier>DOI: 10.1002/mds.28189</identifier><identifier>PMID: 32662532</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; Aspirin ; Genetic factors ; Genetic Predisposition to Disease ; Human health and pathology ; Humans ; Ibuprofen ; Inflammation ; Kinases ; Leucine ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics ; Life Sciences ; LRRK2 protein ; Movement disorders ; Mutation - genetics ; Neurodegenerative diseases ; Nonsteroidal anti-inflammatory drugs ; Parkinson Disease - drug therapy ; Parkinson Disease - genetics ; Parkinson's disease ; Penetrance</subject><ispartof>Movement disorders, 2020-10, Vol.35 (10), p.1755-1764</ispartof><rights>2020 International Parkinson and Movement Disorder Society</rights><rights>2020 International Parkinson and Movement Disorder Society.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4229-83ba761ccb71764f8e065326a313b0c96390f7ce150fc9ee648bf9ac0a68bb63</citedby><cites>FETCH-LOGICAL-c4229-83ba761ccb71764f8e065326a313b0c96390f7ce150fc9ee648bf9ac0a68bb63</cites><orcidid>0000-0002-0941-3990 ; 0000-0001-7325-0199</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmds.28189$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmds.28189$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,781,785,886,1418,27926,27927,45576,45577</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32662532$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-04574532$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>San Luciano, Marta</creatorcontrib><creatorcontrib>Tanner, Caroline M.</creatorcontrib><creatorcontrib>Meng, Cheryl</creatorcontrib><creatorcontrib>Marras, Connie</creatorcontrib><creatorcontrib>Lang, Anthony E.</creatorcontrib><creatorcontrib>Schüle, Birgitt</creatorcontrib><creatorcontrib>Langston, J. William</creatorcontrib><creatorcontrib>Corvol, Jean‐Christophe</creatorcontrib><creatorcontrib>Goldwurm, Stefano</creatorcontrib><creatorcontrib>Berg, Daniela</creatorcontrib><creatorcontrib>Tazir, Meriem</creatorcontrib><creatorcontrib>Mellick, George D.</creatorcontrib><creatorcontrib>Sue, Carolyn M.</creatorcontrib><creatorcontrib>Tan, Eng King</creatorcontrib><creatorcontrib>Bressman, Susan</creatorcontrib><creatorcontrib>Saunders‐Pullman, Rachel</creatorcontrib><creatorcontrib>Raymond, Deborah</creatorcontrib><creatorcontrib>Barrett, Matthew James</creatorcontrib><creatorcontrib>Cabassa, Jose</creatorcontrib><creatorcontrib>Groves, Mark</creatorcontrib><creatorcontrib>Hunt, Ann L</creatorcontrib><creatorcontrib>Lubarr, Naomi</creatorcontrib><creatorcontrib>Palmese, Christina</creatorcontrib><creatorcontrib>Sachdev, Rivka</creatorcontrib><creatorcontrib>Sarva, Harini</creatorcontrib><creatorcontrib>Shanker, Vicki</creatorcontrib><creatorcontrib>Swan, Matthew Carrington</creatorcontrib><creatorcontrib>Soto‐Valencia, Jeannie</creatorcontrib><creatorcontrib>Johannes, Brooke</creatorcontrib><creatorcontrib>Ortega, Robert</creatorcontrib><creatorcontrib>Alcalay, Roy N</creatorcontrib><creatorcontrib>Tang, Ming‐X</creatorcontrib><creatorcontrib>Santana, Helen Mejia</creatorcontrib><creatorcontrib>Orbe‐Reilly, Martha</creatorcontrib><creatorcontrib>Fahn, Stanley</creatorcontrib><creatorcontrib>Cote, Lucien</creatorcontrib><creatorcontrib>Ford, Blair</creatorcontrib><creatorcontrib>Louis, Elan</creatorcontrib><creatorcontrib>Levy, Oren</creatorcontrib><creatorcontrib>Rosado, Llency</creatorcontrib><creatorcontrib>Ruiz, Diana</creatorcontrib><creatorcontrib>Clark, Lorraine</creatorcontrib><creatorcontrib>Marder, Karen S</creatorcontrib><creatorcontrib>Corvol, Jean‐Christophe</creatorcontrib><creatorcontrib>Bonnet, Anne‐Marie</creatorcontrib><creatorcontrib>Welter, Marie‐Laure</creatorcontrib><creatorcontrib>Mesnage, Valerie</creatorcontrib><creatorcontrib>Vidailhet, Marie</creatorcontrib><creatorcontrib>Roze, Emmanuel</creatorcontrib><creatorcontrib>Lacomblez, Lucette</creatorcontrib><creatorcontrib>Grabli, David</creatorcontrib><creatorcontrib>Mart i Masso, Jose Felix</creatorcontrib><creatorcontrib>Mondragon Rezola, Elisabet</creatorcontrib><creatorcontrib>Alustiza, Ainara Estanga</creatorcontrib><creatorcontrib>Pagola, Ana Gorostidi</creatorcontrib><creatorcontrib>Pont‐Sunyer, Claustre</creatorcontrib><creatorcontrib>Rolan, Dolores Vilas</creatorcontrib><creatorcontrib>Fernandez‐Santiago, Ruben</creatorcontrib><creatorcontrib>Quintana, Maria</creatorcontrib><creatorcontrib>Maragall, Laura</creatorcontrib><creatorcontrib>Hentati, Faycal</creatorcontrib><creatorcontrib>Farrer, Matthew</creatorcontrib><creatorcontrib>Duda, John</creatorcontrib><creatorcontrib>Read, Matt</creatorcontrib><creatorcontrib>Gibson, Rachel</creatorcontrib><creatorcontrib>Sassi, Samia Ben</creatorcontrib><creatorcontrib>Zouari, Mourad</creatorcontrib><creatorcontrib>Nabli, Fatma</creatorcontrib><creatorcontrib>Aasly, Jan</creatorcontrib><creatorcontrib>Andersen, Sigrid</creatorcontrib><creatorcontrib>Bertoni, John</creatorcontrib><creatorcontrib>Carter, Julie</creatorcontrib><creatorcontrib>Elmer, Lawrence</creatorcontrib><creatorcontrib>Jimenez, Nestor Galvez</creatorcontrib><creatorcontrib>Martin, Wayne</creatorcontrib><creatorcontrib>Pahwa, Rajesh</creatorcontrib><creatorcontrib>Lyons, Kelly</creatorcontrib><creatorcontrib>Reich, Stephen</creatorcontrib><creatorcontrib>Ramos, Carmen Serrano</creatorcontrib><creatorcontrib>Wojcieszek, Joanne</creatorcontrib><creatorcontrib>Gurevich, Tanya</creatorcontrib><creatorcontrib>Shira, Anat Bar</creatorcontrib><creatorcontrib>Weisz, Mali Gana</creatorcontrib><creatorcontrib>Yasinovsky, Kira</creatorcontrib><creatorcontrib>Zalis, Maayan</creatorcontrib><creatorcontrib>Thaler, Avner</creatorcontrib><creatorcontrib>Orr‐Urtreger, Avi</creatorcontrib><creatorcontrib>Giladi, Nir</creatorcontrib><creatorcontrib>Mountain, Joanna</creatorcontrib><creatorcontrib>Mestre, Tiago</creatorcontrib><creatorcontrib>Ghate, Taneera</creatorcontrib><creatorcontrib>Singerman, Jennifer</creatorcontrib><creatorcontrib>Al Dakheel, Amaal</creatorcontrib><creatorcontrib>Connolly, Barbara S</creatorcontrib><creatorcontrib>Gasser, Thomas</creatorcontrib><creatorcontrib>Brockmann, Kathrin</creatorcontrib><creatorcontrib>Mullins, Meghan E</creatorcontrib><creatorcontrib>Northover, Carrie</creatorcontrib><creatorcontrib>Facheris, Maurizio</creatorcontrib><creatorcontrib>Fiske, Brian</creatorcontrib><creatorcontrib>Michael J. Fox Foundation LRRK2 Cohort Consortium</creatorcontrib><creatorcontrib>the Michael J. Fox Foundation LRRK2 Cohort Consortium</creatorcontrib><title>Nonsteroidal Anti‐inflammatory Use and LRRK2 Parkinson's Disease Penetrance</title><title>Movement disorders</title><addtitle>Mov Disord</addtitle><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</description><subject>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</subject><subject>Aspirin</subject><subject>Genetic factors</subject><subject>Genetic Predisposition to Disease</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Ibuprofen</subject><subject>Inflammation</subject><subject>Kinases</subject><subject>Leucine</subject><subject>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics</subject><subject>Life Sciences</subject><subject>LRRK2 protein</subject><subject>Movement disorders</subject><subject>Mutation - genetics</subject><subject>Neurodegenerative diseases</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Parkinson Disease - drug therapy</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson's disease</subject><subject>Penetrance</subject><issn>0885-3185</issn><issn>1531-8257</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtOwkAUQCdGI4gu_AHTxIVxUZhHZzpdElAxFiWI68l0mMZiO8WZomHnJ_iNfonFIq5c3eTek5ObA8Apgl0EIe4Vc9fFHPFoD7QRJcjnmIb7oA05pz5BnLbAkXMLCBGiiB2CFsGMYUpwG4zvS-MqbctsLnOvb6rs6-MzM2kui0JWpV17T0570sy9eDq9w95E2pfMuNJcOG-YOS3r60QbXVlplD4GB6nMnT7Zzg6YXV_NBiM_fri5HfRjXwUYRz4niQwZUioJUciClGvI6m-YJIgkUEWMRDANlUYUpirSmgU8SSOpoGQ8SRjpgMtG-yxzsbRZIe1alDITo34sNjsY0DCojW-oZs8bdmnL15V2lViUK2vq7wQOKKIB42H4Z1S2dM7qdKdFUGwai7qx-Glcs2db4yop9HxH_katgV4DvGe5Xv9vEuPhY6P8BhtHhLY</recordid><startdate>202010</startdate><enddate>202010</enddate><creator>San Luciano, Marta</creator><creator>Tanner, Caroline M.</creator><creator>Meng, Cheryl</creator><creator>Marras, Connie</creator><creator>Lang, Anthony E.</creator><creator>Schüle, Birgitt</creator><creator>Langston, J. William</creator><creator>Corvol, Jean‐Christophe</creator><creator>Goldwurm, Stefano</creator><creator>Berg, Daniela</creator><creator>Tazir, Meriem</creator><creator>Mellick, George D.</creator><creator>Sue, Carolyn M.</creator><creator>Tan, Eng King</creator><creator>Bressman, Susan</creator><creator>Saunders‐Pullman, Rachel</creator><creator>Raymond, Deborah</creator><creator>Barrett, Matthew James</creator><creator>Cabassa, Jose</creator><creator>Groves, Mark</creator><creator>Hunt, Ann L</creator><creator>Lubarr, Naomi</creator><creator>Palmese, Christina</creator><creator>Sachdev, Rivka</creator><creator>Sarva, Harini</creator><creator>Shanker, Vicki</creator><creator>Swan, Matthew Carrington</creator><creator>Soto‐Valencia, Jeannie</creator><creator>Johannes, Brooke</creator><creator>Ortega, Robert</creator><creator>Alcalay, Roy N</creator><creator>Tang, Ming‐X</creator><creator>Santana, Helen Mejia</creator><creator>Orbe‐Reilly, Martha</creator><creator>Fahn, Stanley</creator><creator>Cote, Lucien</creator><creator>Ford, Blair</creator><creator>Louis, Elan</creator><creator>Levy, Oren</creator><creator>Rosado, Llency</creator><creator>Ruiz, Diana</creator><creator>Clark, Lorraine</creator><creator>Marder, Karen S</creator><creator>Corvol, Jean‐Christophe</creator><creator>Bonnet, Anne‐Marie</creator><creator>Welter, Marie‐Laure</creator><creator>Mesnage, Valerie</creator><creator>Vidailhet, Marie</creator><creator>Roze, Emmanuel</creator><creator>Lacomblez, Lucette</creator><creator>Grabli, David</creator><creator>Mart i Masso, Jose Felix</creator><creator>Mondragon Rezola, Elisabet</creator><creator>Alustiza, Ainara Estanga</creator><creator>Pagola, Ana Gorostidi</creator><creator>Pont‐Sunyer, Claustre</creator><creator>Rolan, Dolores Vilas</creator><creator>Fernandez‐Santiago, Ruben</creator><creator>Quintana, Maria</creator><creator>Maragall, Laura</creator><creator>Hentati, Faycal</creator><creator>Farrer, Matthew</creator><creator>Duda, John</creator><creator>Read, Matt</creator><creator>Gibson, Rachel</creator><creator>Sassi, Samia Ben</creator><creator>Zouari, Mourad</creator><creator>Nabli, Fatma</creator><creator>Aasly, Jan</creator><creator>Andersen, Sigrid</creator><creator>Bertoni, John</creator><creator>Carter, Julie</creator><creator>Elmer, Lawrence</creator><creator>Jimenez, Nestor Galvez</creator><creator>Martin, Wayne</creator><creator>Pahwa, Rajesh</creator><creator>Lyons, Kelly</creator><creator>Reich, Stephen</creator><creator>Ramos, Carmen Serrano</creator><creator>Wojcieszek, Joanne</creator><creator>Gurevich, Tanya</creator><creator>Shira, Anat Bar</creator><creator>Weisz, Mali Gana</creator><creator>Yasinovsky, Kira</creator><creator>Zalis, Maayan</creator><creator>Thaler, Avner</creator><creator>Orr‐Urtreger, Avi</creator><creator>Giladi, Nir</creator><creator>Mountain, Joanna</creator><creator>Mestre, Tiago</creator><creator>Ghate, Taneera</creator><creator>Singerman, Jennifer</creator><creator>Al Dakheel, Amaal</creator><creator>Connolly, Barbara S</creator><creator>Gasser, Thomas</creator><creator>Brockmann, Kathrin</creator><creator>Mullins, Meghan E</creator><creator>Northover, Carrie</creator><creator>Facheris, Maurizio</creator><creator>Fiske, Brian</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><general>Wiley</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-0941-3990</orcidid><orcidid>https://orcid.org/0000-0001-7325-0199</orcidid></search><sort><creationdate>202010</creationdate><title>Nonsteroidal Anti‐inflammatory Use and LRRK2 Parkinson's Disease Penetrance</title><author>San Luciano, Marta ; Tanner, Caroline M. ; Meng, Cheryl ; Marras, Connie ; Lang, Anthony E. ; Schüle, Birgitt ; Langston, J. William ; Corvol, Jean‐Christophe ; Goldwurm, Stefano ; Berg, Daniela ; Tazir, Meriem ; Mellick, George D. ; Sue, Carolyn M. ; Tan, Eng King ; Bressman, Susan ; Saunders‐Pullman, Rachel ; Raymond, Deborah ; Barrett, Matthew James ; Cabassa, Jose ; Groves, Mark ; Hunt, Ann L ; Lubarr, Naomi ; Palmese, Christina ; Sachdev, Rivka ; Sarva, Harini ; Shanker, Vicki ; Swan, Matthew Carrington ; Soto‐Valencia, Jeannie ; Johannes, Brooke ; Ortega, Robert ; Alcalay, Roy N ; Tang, Ming‐X ; Santana, Helen Mejia ; Orbe‐Reilly, Martha ; Fahn, Stanley ; Cote, Lucien ; Ford, Blair ; Louis, Elan ; Levy, Oren ; Rosado, Llency ; Ruiz, Diana ; Clark, Lorraine ; Marder, Karen S ; Corvol, Jean‐Christophe ; Bonnet, Anne‐Marie ; Welter, Marie‐Laure ; Mesnage, Valerie ; Vidailhet, Marie ; Roze, Emmanuel ; Lacomblez, Lucette ; Grabli, David ; Mart i Masso, Jose Felix ; Mondragon Rezola, Elisabet ; Alustiza, Ainara Estanga ; Pagola, Ana Gorostidi ; Pont‐Sunyer, Claustre ; Rolan, Dolores Vilas ; Fernandez‐Santiago, Ruben ; Quintana, Maria ; Maragall, Laura ; Hentati, Faycal ; Farrer, Matthew ; Duda, John ; Read, Matt ; Gibson, Rachel ; Sassi, Samia Ben ; Zouari, Mourad ; Nabli, Fatma ; Aasly, Jan ; Andersen, Sigrid ; Bertoni, John ; Carter, Julie ; Elmer, Lawrence ; Jimenez, Nestor Galvez ; Martin, Wayne ; Pahwa, Rajesh ; Lyons, Kelly ; Reich, Stephen ; Ramos, Carmen Serrano ; Wojcieszek, Joanne ; Gurevich, Tanya ; Shira, Anat Bar ; Weisz, Mali Gana ; Yasinovsky, Kira ; Zalis, Maayan ; Thaler, Avner ; Orr‐Urtreger, Avi ; Giladi, Nir ; Mountain, Joanna ; Mestre, Tiago ; Ghate, Taneera ; Singerman, Jennifer ; Al Dakheel, Amaal ; Connolly, Barbara S ; Gasser, Thomas ; Brockmann, Kathrin ; Mullins, Meghan E ; Northover, Carrie ; Facheris, Maurizio ; Fiske, Brian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4229-83ba761ccb71764f8e065326a313b0c96390f7ce150fc9ee648bf9ac0a68bb63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</topic><topic>Aspirin</topic><topic>Genetic factors</topic><topic>Genetic Predisposition to Disease</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Ibuprofen</topic><topic>Inflammation</topic><topic>Kinases</topic><topic>Leucine</topic><topic>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics</topic><topic>Life Sciences</topic><topic>LRRK2 protein</topic><topic>Movement disorders</topic><topic>Mutation - genetics</topic><topic>Neurodegenerative diseases</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>Parkinson Disease - drug therapy</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson's disease</topic><topic>Penetrance</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>San Luciano, Marta</creatorcontrib><creatorcontrib>Tanner, Caroline M.</creatorcontrib><creatorcontrib>Meng, Cheryl</creatorcontrib><creatorcontrib>Marras, Connie</creatorcontrib><creatorcontrib>Lang, Anthony E.</creatorcontrib><creatorcontrib>Schüle, Birgitt</creatorcontrib><creatorcontrib>Langston, J. William</creatorcontrib><creatorcontrib>Corvol, Jean‐Christophe</creatorcontrib><creatorcontrib>Goldwurm, Stefano</creatorcontrib><creatorcontrib>Berg, Daniela</creatorcontrib><creatorcontrib>Tazir, Meriem</creatorcontrib><creatorcontrib>Mellick, George D.</creatorcontrib><creatorcontrib>Sue, Carolyn M.</creatorcontrib><creatorcontrib>Tan, Eng King</creatorcontrib><creatorcontrib>Bressman, Susan</creatorcontrib><creatorcontrib>Saunders‐Pullman, Rachel</creatorcontrib><creatorcontrib>Raymond, Deborah</creatorcontrib><creatorcontrib>Barrett, Matthew James</creatorcontrib><creatorcontrib>Cabassa, Jose</creatorcontrib><creatorcontrib>Groves, Mark</creatorcontrib><creatorcontrib>Hunt, Ann L</creatorcontrib><creatorcontrib>Lubarr, Naomi</creatorcontrib><creatorcontrib>Palmese, Christina</creatorcontrib><creatorcontrib>Sachdev, Rivka</creatorcontrib><creatorcontrib>Sarva, Harini</creatorcontrib><creatorcontrib>Shanker, Vicki</creatorcontrib><creatorcontrib>Swan, Matthew Carrington</creatorcontrib><creatorcontrib>Soto‐Valencia, Jeannie</creatorcontrib><creatorcontrib>Johannes, Brooke</creatorcontrib><creatorcontrib>Ortega, Robert</creatorcontrib><creatorcontrib>Alcalay, Roy N</creatorcontrib><creatorcontrib>Tang, Ming‐X</creatorcontrib><creatorcontrib>Santana, Helen Mejia</creatorcontrib><creatorcontrib>Orbe‐Reilly, Martha</creatorcontrib><creatorcontrib>Fahn, Stanley</creatorcontrib><creatorcontrib>Cote, Lucien</creatorcontrib><creatorcontrib>Ford, Blair</creatorcontrib><creatorcontrib>Louis, Elan</creatorcontrib><creatorcontrib>Levy, Oren</creatorcontrib><creatorcontrib>Rosado, Llency</creatorcontrib><creatorcontrib>Ruiz, Diana</creatorcontrib><creatorcontrib>Clark, Lorraine</creatorcontrib><creatorcontrib>Marder, Karen S</creatorcontrib><creatorcontrib>Corvol, Jean‐Christophe</creatorcontrib><creatorcontrib>Bonnet, Anne‐Marie</creatorcontrib><creatorcontrib>Welter, Marie‐Laure</creatorcontrib><creatorcontrib>Mesnage, Valerie</creatorcontrib><creatorcontrib>Vidailhet, Marie</creatorcontrib><creatorcontrib>Roze, Emmanuel</creatorcontrib><creatorcontrib>Lacomblez, Lucette</creatorcontrib><creatorcontrib>Grabli, David</creatorcontrib><creatorcontrib>Mart i Masso, Jose Felix</creatorcontrib><creatorcontrib>Mondragon Rezola, Elisabet</creatorcontrib><creatorcontrib>Alustiza, Ainara Estanga</creatorcontrib><creatorcontrib>Pagola, Ana Gorostidi</creatorcontrib><creatorcontrib>Pont‐Sunyer, Claustre</creatorcontrib><creatorcontrib>Rolan, Dolores Vilas</creatorcontrib><creatorcontrib>Fernandez‐Santiago, Ruben</creatorcontrib><creatorcontrib>Quintana, Maria</creatorcontrib><creatorcontrib>Maragall, Laura</creatorcontrib><creatorcontrib>Hentati, Faycal</creatorcontrib><creatorcontrib>Farrer, Matthew</creatorcontrib><creatorcontrib>Duda, John</creatorcontrib><creatorcontrib>Read, Matt</creatorcontrib><creatorcontrib>Gibson, Rachel</creatorcontrib><creatorcontrib>Sassi, Samia Ben</creatorcontrib><creatorcontrib>Zouari, Mourad</creatorcontrib><creatorcontrib>Nabli, Fatma</creatorcontrib><creatorcontrib>Aasly, Jan</creatorcontrib><creatorcontrib>Andersen, Sigrid</creatorcontrib><creatorcontrib>Bertoni, John</creatorcontrib><creatorcontrib>Carter, Julie</creatorcontrib><creatorcontrib>Elmer, Lawrence</creatorcontrib><creatorcontrib>Jimenez, Nestor Galvez</creatorcontrib><creatorcontrib>Martin, Wayne</creatorcontrib><creatorcontrib>Pahwa, Rajesh</creatorcontrib><creatorcontrib>Lyons, Kelly</creatorcontrib><creatorcontrib>Reich, Stephen</creatorcontrib><creatorcontrib>Ramos, Carmen Serrano</creatorcontrib><creatorcontrib>Wojcieszek, Joanne</creatorcontrib><creatorcontrib>Gurevich, Tanya</creatorcontrib><creatorcontrib>Shira, Anat Bar</creatorcontrib><creatorcontrib>Weisz, Mali Gana</creatorcontrib><creatorcontrib>Yasinovsky, Kira</creatorcontrib><creatorcontrib>Zalis, Maayan</creatorcontrib><creatorcontrib>Thaler, Avner</creatorcontrib><creatorcontrib>Orr‐Urtreger, Avi</creatorcontrib><creatorcontrib>Giladi, Nir</creatorcontrib><creatorcontrib>Mountain, Joanna</creatorcontrib><creatorcontrib>Mestre, Tiago</creatorcontrib><creatorcontrib>Ghate, Taneera</creatorcontrib><creatorcontrib>Singerman, Jennifer</creatorcontrib><creatorcontrib>Al Dakheel, Amaal</creatorcontrib><creatorcontrib>Connolly, Barbara S</creatorcontrib><creatorcontrib>Gasser, Thomas</creatorcontrib><creatorcontrib>Brockmann, Kathrin</creatorcontrib><creatorcontrib>Mullins, Meghan E</creatorcontrib><creatorcontrib>Northover, Carrie</creatorcontrib><creatorcontrib>Facheris, Maurizio</creatorcontrib><creatorcontrib>Fiske, Brian</creatorcontrib><creatorcontrib>Michael J. Fox Foundation LRRK2 Cohort Consortium</creatorcontrib><creatorcontrib>the Michael J. Fox Foundation LRRK2 Cohort Consortium</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Movement disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>San Luciano, Marta</au><au>Tanner, Caroline M.</au><au>Meng, Cheryl</au><au>Marras, Connie</au><au>Lang, Anthony E.</au><au>Schüle, Birgitt</au><au>Langston, J. William</au><au>Corvol, Jean‐Christophe</au><au>Goldwurm, Stefano</au><au>Berg, Daniela</au><au>Tazir, Meriem</au><au>Mellick, George D.</au><au>Sue, Carolyn M.</au><au>Tan, Eng King</au><au>Bressman, Susan</au><au>Saunders‐Pullman, Rachel</au><au>Raymond, Deborah</au><au>Barrett, Matthew James</au><au>Cabassa, Jose</au><au>Groves, Mark</au><au>Hunt, Ann L</au><au>Lubarr, Naomi</au><au>Palmese, Christina</au><au>Sachdev, Rivka</au><au>Sarva, Harini</au><au>Shanker, Vicki</au><au>Swan, Matthew Carrington</au><au>Soto‐Valencia, Jeannie</au><au>Johannes, Brooke</au><au>Ortega, Robert</au><au>Alcalay, Roy N</au><au>Tang, Ming‐X</au><au>Santana, Helen Mejia</au><au>Orbe‐Reilly, Martha</au><au>Fahn, Stanley</au><au>Cote, Lucien</au><au>Ford, Blair</au><au>Louis, Elan</au><au>Levy, Oren</au><au>Rosado, Llency</au><au>Ruiz, Diana</au><au>Clark, Lorraine</au><au>Marder, Karen S</au><au>Corvol, Jean‐Christophe</au><au>Bonnet, Anne‐Marie</au><au>Welter, Marie‐Laure</au><au>Mesnage, Valerie</au><au>Vidailhet, Marie</au><au>Roze, Emmanuel</au><au>Lacomblez, Lucette</au><au>Grabli, David</au><au>Mart i Masso, Jose Felix</au><au>Mondragon Rezola, Elisabet</au><au>Alustiza, Ainara Estanga</au><au>Pagola, Ana Gorostidi</au><au>Pont‐Sunyer, Claustre</au><au>Rolan, Dolores Vilas</au><au>Fernandez‐Santiago, Ruben</au><au>Quintana, Maria</au><au>Maragall, Laura</au><au>Hentati, Faycal</au><au>Farrer, Matthew</au><au>Duda, John</au><au>Read, Matt</au><au>Gibson, Rachel</au><au>Sassi, Samia Ben</au><au>Zouari, Mourad</au><au>Nabli, Fatma</au><au>Aasly, Jan</au><au>Andersen, Sigrid</au><au>Bertoni, John</au><au>Carter, Julie</au><au>Elmer, Lawrence</au><au>Jimenez, Nestor Galvez</au><au>Martin, Wayne</au><au>Pahwa, Rajesh</au><au>Lyons, Kelly</au><au>Reich, Stephen</au><au>Ramos, Carmen Serrano</au><au>Wojcieszek, Joanne</au><au>Gurevich, Tanya</au><au>Shira, Anat Bar</au><au>Weisz, Mali Gana</au><au>Yasinovsky, Kira</au><au>Zalis, Maayan</au><au>Thaler, Avner</au><au>Orr‐Urtreger, Avi</au><au>Giladi, Nir</au><au>Mountain, Joanna</au><au>Mestre, Tiago</au><au>Ghate, Taneera</au><au>Singerman, Jennifer</au><au>Al Dakheel, Amaal</au><au>Connolly, Barbara S</au><au>Gasser, Thomas</au><au>Brockmann, Kathrin</au><au>Mullins, Meghan E</au><au>Northover, Carrie</au><au>Facheris, Maurizio</au><au>Fiske, Brian</au><aucorp>Michael J. Fox Foundation LRRK2 Cohort Consortium</aucorp><aucorp>the Michael J. Fox Foundation LRRK2 Cohort Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nonsteroidal Anti‐inflammatory Use and LRRK2 Parkinson's Disease Penetrance</atitle><jtitle>Movement disorders</jtitle><addtitle>Mov Disord</addtitle><date>2020-10</date><risdate>2020</risdate><volume>35</volume><issue>10</issue><spage>1755</spage><epage>1764</epage><pages>1755-1764</pages><issn>0885-3185</issn><eissn>1531-8257</eissn><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</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>32662532</pmid><doi>10.1002/mds.28189</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0941-3990</orcidid><orcidid>https://orcid.org/0000-0001-7325-0199</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0885-3185 |
| ispartof | Movement disorders, 2020-10, Vol.35 (10), p.1755-1764 |
| issn | 0885-3185 1531-8257 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_04574532v1 |
| source | MEDLINE; Wiley Online Library All Journals |
| subjects | Anti-Inflammatory Agents, Non-Steroidal - therapeutic use Aspirin Genetic factors Genetic Predisposition to Disease Human health and pathology Humans Ibuprofen Inflammation Kinases Leucine Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics Life Sciences LRRK2 protein Movement disorders Mutation - genetics Neurodegenerative diseases Nonsteroidal anti-inflammatory drugs Parkinson Disease - drug therapy Parkinson Disease - genetics Parkinson's disease Penetrance |
| title | Nonsteroidal Anti‐inflammatory Use and LRRK2 Parkinson's Disease Penetrance |
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