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Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease
OBJECTIVE: To evaluate sex differences and the relative effect of G2019S LRRK2 mutations in Parkinson's disease (PD). METHODS: 530 LRRK2 PD carriers and 759 noncarrier PD (idiopathic, IPD) evaluated as part of the Fox Foundation (MJFF) Consortium were included. All participants completed a stud...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682117/ https://www.ncbi.nlm.nih.gov/pubmed/29159192 http://dx.doi.org/10.1002/acn3.489 |
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author | San Luciano, Marta Wang, Cuiling Ortega, Roberto A. Giladi, Nir Marder, Karen Bressman, Susan Saunders‐Pullman, Rachel |
author_facet | San Luciano, Marta Wang, Cuiling Ortega, Roberto A. Giladi, Nir Marder, Karen Bressman, Susan Saunders‐Pullman, Rachel |
author_sort | San Luciano, Marta |
collection | PubMed |
description | OBJECTIVE: To evaluate sex differences and the relative effect of G2019S LRRK2 mutations in Parkinson's disease (PD). METHODS: 530 LRRK2 PD carriers and 759 noncarrier PD (idiopathic, IPD) evaluated as part of the Fox Foundation (MJFF) Consortium were included. All participants completed a study visit including information on clinical features, treatment, examination, and motor and nonmotor questionnaires. Clinical features were compared between men and women separately for IPD and LRRK2 PD; and features were compared between IPD and LRRK2 PD separately for men and women. RESULTS: Among IPD: men had higher levodopa equivalency dose (LED), worse activities of daily living and motoric severity but lower complications of therapy (UPDRS‐IV). IPD women had higher olfaction and thermoregulatory scores and were more likely to report family history of PD. Among LRRK2 PD: Male predominance was not observed among G2019S LRRK2 cases. Women had worse UPDRS‐IV but better olfaction. Among same sex:LRRK2 men and women had better olfaction than IPD counterparts. LRRK2 men demonstrated lower motor and higher cognitive, RBD and thermoregulation scores than IPD men and LRRK2 women had greater UDPRS‐IV and rates of dyskinesia. INTERPRETATION: There were clinical differences between sexes with a more severe phenotype in IPD men and more complications of therapy in women. The more severe male phenotype was moderated by LRRK2, with LRRK2 men and women showing less diversity of phenotype. Our study supports that both genetics and sex drive phenotype, and thus trials in LRRK2 and IPD should consider gender stratification in design or analysis. |
format | Online Article Text |
id | pubmed-5682117 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56821172017-11-20 Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease San Luciano, Marta Wang, Cuiling Ortega, Roberto A. Giladi, Nir Marder, Karen Bressman, Susan Saunders‐Pullman, Rachel Ann Clin Transl Neurol Research Articles OBJECTIVE: To evaluate sex differences and the relative effect of G2019S LRRK2 mutations in Parkinson's disease (PD). METHODS: 530 LRRK2 PD carriers and 759 noncarrier PD (idiopathic, IPD) evaluated as part of the Fox Foundation (MJFF) Consortium were included. All participants completed a study visit including information on clinical features, treatment, examination, and motor and nonmotor questionnaires. Clinical features were compared between men and women separately for IPD and LRRK2 PD; and features were compared between IPD and LRRK2 PD separately for men and women. RESULTS: Among IPD: men had higher levodopa equivalency dose (LED), worse activities of daily living and motoric severity but lower complications of therapy (UPDRS‐IV). IPD women had higher olfaction and thermoregulatory scores and were more likely to report family history of PD. Among LRRK2 PD: Male predominance was not observed among G2019S LRRK2 cases. Women had worse UPDRS‐IV but better olfaction. Among same sex:LRRK2 men and women had better olfaction than IPD counterparts. LRRK2 men demonstrated lower motor and higher cognitive, RBD and thermoregulation scores than IPD men and LRRK2 women had greater UDPRS‐IV and rates of dyskinesia. INTERPRETATION: There were clinical differences between sexes with a more severe phenotype in IPD men and more complications of therapy in women. The more severe male phenotype was moderated by LRRK2, with LRRK2 men and women showing less diversity of phenotype. Our study supports that both genetics and sex drive phenotype, and thus trials in LRRK2 and IPD should consider gender stratification in design or analysis. John Wiley and Sons Inc. 2017-10-19 /pmc/articles/PMC5682117/ /pubmed/29159192 http://dx.doi.org/10.1002/acn3.489 Text en © 2017 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles San Luciano, Marta Wang, Cuiling Ortega, Roberto A. Giladi, Nir Marder, Karen Bressman, Susan Saunders‐Pullman, Rachel Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease |
title | Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease |
title_full | Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease |
title_fullStr | Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease |
title_full_unstemmed | Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease |
title_short | Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease |
title_sort | sex differences in lrrk2 g2019s and idiopathic parkinson's disease |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682117/ https://www.ncbi.nlm.nih.gov/pubmed/29159192 http://dx.doi.org/10.1002/acn3.489 |
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