Ashley F Curtis1, Mario Masellis1, Ging-Yuek Robin Hsiung1, Rahim Moineddin1, Kathy Zhang1, Bonnie Au1, Geneva Millett1, Ian Mackenzie1, Ekaterina Rogaeva1, Mary C Tierney2. 1. From the Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute (A.F.C., M.M., K.Z., M.C.T.), Primary Care Research Unit (A.F.C., K.Z., B.A., G.M., M.C.T.), and Cognitive & Movement Disorders Clinic (M.M.), Sunnybrook Health Sciences Center, Toronto; Division of Neurology (G.-Y.R.H.) and Department of Pathology and Laboratory Medicine (I.M.), University of British Columbia, Vancouver; Departments of Family and Community Medicine (R.M., M.C.T.) and Medicine (E.R.) and Tanz Centre for Research in Neurodegenerative Diseases (E.R.), University of Toronto; and Department of Neuropathology (I.M.), Vancouver General Hospital, Canada. 2. From the Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute (A.F.C., M.M., K.Z., M.C.T.), Primary Care Research Unit (A.F.C., K.Z., B.A., G.M., M.C.T.), and Cognitive & Movement Disorders Clinic (M.M.), Sunnybrook Health Sciences Center, Toronto; Division of Neurology (G.-Y.R.H.) and Department of Pathology and Laboratory Medicine (I.M.), University of British Columbia, Vancouver; Departments of Family and Community Medicine (R.M., M.C.T.) and Medicine (E.R.) and Tanz Centre for Research in Neurodegenerative Diseases (E.R.), University of Toronto; and Department of Neuropathology (I.M.), Vancouver General Hospital, Canada. mary.tierney@sunnybrook.ca.
Abstract
OBJECTIVE: To conduct a meta-analysis that investigates sex differences in the prevalence of mutations in the 3 most common genes that cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)-chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT)-in patients clinically diagnosed with these conditions. METHODS: MEDLINE, EMBASE, and PsycINFO databases were searched (inception to June 30, 2016). Studies of patients with FTD or ALS that reported the number of men and women with and without mutations of interest were selected. Female to male pooled risk ratios (RR) and 95% confidence intervals (CI) for each mutation were calculated using random-effects models. RESULTS: Thirty-two articles reporting 12,784 patients with ALS (including 1,244 C9orf72 mutation carriers) revealed a higher prevalence of female patients with C9orf72-related ALS (RR 1.16, 95% CI 1.04-1.29). Twenty-three articles reporting 5,320 patients with FTD (including 488 C9orf72 mutation carriers) revealed no sex differences in C9orf72-related FTD (RR 0.95, 95% CI 0.81-1.12). Thirty-six articles reporting 3,857 patients with FTD (including 369 GRN mutation carriers) revealed a higher prevalence of female patients with GRN-related FTD (RR 1.33, 95% CI 1.09-1.62). Finally, 21 articles reporting 2,377 patients with FTD (including 215 MAPT mutation carriers) revealed no sex difference in MAPT-related FTD (RR 1.21, 95% CI 0.95-1.55). CONCLUSIONS: Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN-mediated phenotypic expression.
OBJECTIVE: To conduct a meta-analysis that investigates sex differences in the prevalence of mutations in the 3 most common genes that cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)-chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT)-in patients clinically diagnosed with these conditions. METHODS: MEDLINE, EMBASE, and PsycINFO databases were searched (inception to June 30, 2016). Studies of patients with FTD or ALS that reported the number of men and women with and without mutations of interest were selected. Female to male pooled risk ratios (RR) and 95% confidence intervals (CI) for each mutation were calculated using random-effects models. RESULTS: Thirty-two articles reporting 12,784 patients with ALS (including 1,244 C9orf72 mutation carriers) revealed a higher prevalence of female patients with C9orf72-related ALS (RR 1.16, 95% CI 1.04-1.29). Twenty-three articles reporting 5,320 patients with FTD (including 488 C9orf72 mutation carriers) revealed no sex differences in C9orf72-related FTD (RR 0.95, 95% CI 0.81-1.12). Thirty-six articles reporting 3,857 patients with FTD (including 369 GRN mutation carriers) revealed a higher prevalence of female patients with GRN-related FTD (RR 1.33, 95% CI 1.09-1.62). Finally, 21 articles reporting 2,377 patients with FTD (including 215 MAPT mutation carriers) revealed no sex difference in MAPT-related FTD (RR 1.21, 95% CI 0.95-1.55). CONCLUSIONS: Higher female prevalence of C9orf72hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN-mediated phenotypic expression.
Authors: Maria Luisa Gorno-Tempini; Nina F Dronkers; Katherine P Rankin; Jennifer M Ogar; La Phengrasamy; Howard J Rosen; Julene K Johnson; Michael W Weiner; Bruce L Miller Journal: Ann Neurol Date: 2004-03 Impact factor: 10.422
Authors: Kevin P Kenna; Russell L McLaughlin; Susan Byrne; Marwa Elamin; Mark Heverin; Elaine M Kenny; Paul Cormican; Derek W Morris; Colette G Donaghy; Daniel G Bradley; Orla Hardiman Journal: J Med Genet Date: 2013-07-23 Impact factor: 6.318