학술논문
Differences in Sex-Specific Frequency of Glucocerebrosidase Variant Carriers and Familial Parkinsonism.
Document Type
Academic Journal
Author
Ortega RA; Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.; Bressman SB; Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.; Raymond D; Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.; Ozelius LJ; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Katsnelson V; Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.; Leaver K; Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.; Swan MC; Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.; Shanker V; Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.; Miravite J; Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.; Wang C; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.; Bennett SAL; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, Ottawa Institute of Systems Biology, University of Brain and Mind Research Institute, University of Ottawa, Ottawa, Ontario, Canada.; Saunders-Pullman R; Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.
Source
Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8610688 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-8257 (Electronic) Linking ISSN: 08853185 NLM ISO Abbreviation: Mov Disord Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Although men and women with the LRRK2 G2019S variant appear to be equally likely to have Parkinson's disease (PD), the sex-distribution among glucocerebrosidase (GBA) variant carriers with PD, including limited to specific variant severities of GBA, is not well understood. Further, the sex-specific genetic contribution to PD without a known genetic variant is controversial.
Objectives: To better understand sex differences in genetic contribution to PD, especially sex-specific frequencies among GBA variant carriers with PD (GBA PD) and LRRK2-G2019S variant carriers with PD (LRRK2 PD).
Methods: We assess differences in the sex-specific frequency in GBA PD, including in subsets of GBA variant severity, LRRK2 PD, and idiopathic PD in an Ashkenazi Jewish cohort with PD. Further, we expand prior work evaluating differences in family history of parkinsonism.
Results: Both idiopathic PD (267/420 men, 63.6%) (P < 0.001) and GBA PD overall (64/107, 59.8%) (P = 0.042) were more likely to be men, whereas no difference was seen in LRRK2 PD (50/99, 50.5%) and LRRK2/GBA PD (5/10, 50%). However, among GBA PD probands, severe variant carriers were more likely to be women (15/19 women, 79.0%) (P = 0.005), whereas mild variant carriers (44/70 men, 62.9%) (P = 0.039) and risk-variant carriers (15/17 men, 88.2%) (P = 0.001) were more likely to be men.
Conclusions: Our study demonstrates that the male-sex predominance present in GBA PD overall was not consistent across GBA variant severities, and a female-sex predominance was present among severe GBA variant carriers. Therefore, research and trial designs for PD should consider sex-specific differences, including across GBA variant severities. © 2022 International Parkinson and Movement Disorder Society.
(© 2022 International Parkinson and Movement Disorder Society.)
Objectives: To better understand sex differences in genetic contribution to PD, especially sex-specific frequencies among GBA variant carriers with PD (GBA PD) and LRRK2-G2019S variant carriers with PD (LRRK2 PD).
Methods: We assess differences in the sex-specific frequency in GBA PD, including in subsets of GBA variant severity, LRRK2 PD, and idiopathic PD in an Ashkenazi Jewish cohort with PD. Further, we expand prior work evaluating differences in family history of parkinsonism.
Results: Both idiopathic PD (267/420 men, 63.6%) (P < 0.001) and GBA PD overall (64/107, 59.8%) (P = 0.042) were more likely to be men, whereas no difference was seen in LRRK2 PD (50/99, 50.5%) and LRRK2/GBA PD (5/10, 50%). However, among GBA PD probands, severe variant carriers were more likely to be women (15/19 women, 79.0%) (P = 0.005), whereas mild variant carriers (44/70 men, 62.9%) (P = 0.039) and risk-variant carriers (15/17 men, 88.2%) (P = 0.001) were more likely to be men.
Conclusions: Our study demonstrates that the male-sex predominance present in GBA PD overall was not consistent across GBA variant severities, and a female-sex predominance was present among severe GBA variant carriers. Therefore, research and trial designs for PD should consider sex-specific differences, including across GBA variant severities. © 2022 International Parkinson and Movement Disorder Society.
(© 2022 International Parkinson and Movement Disorder Society.)