No association of CpG SNP rs9357140 with onset age in Belgian C9orf72 repeat expansion carriers

NEUROBIOLOGY OF AGING

卷:97

Article

Kocog, Cemile^1,2  Gossye, Helena^{1,2,3,4,6,7,8}  Dillen, Lubina^1,2  Van Mossevelde, Sara^1,2,3,6,7,8  De Bleecker, Jan L.⁹  Vandenberghe, Rik^10,11  De Deyn, Peter P.^2,6,7,8  Sleegers, Kristel^1,2  Cras, Patrick^2,3  Engelborghs, Sebastiaan^2,4,5  Van Broeckhoven, Christine^1,2  van der Zee, Julie^1,2 

[1] VIB, Ctr Mol Neurol, Neurodegenerat Brain Dis Grp, Antwerp, Belgium

[2] Univ Antwerp, Inst Born Bunge, Lab Neurogenet, Antwerp, Belgium

[3] Antwerp Univ Hosp, Dept Neurol, Antwerp, Belgium

[4] UZ Brussel, Dept Neurol, Brussels, Belgium

[5] UZ Brussel, Ctr Neurosci, Brussels, Belgium

[6] Vrije Univ Brussel, Brussels, Belgium

[7] Hosp Network Antwerp, Dept Neurol, Antwerp, Belgium

[8] Hosp Network Antwerp, Memory Clin, Antwerp, Belgium

[9] Ghent Univ Hosp, Dept Neurol, Ghent, Belgium

[10] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium

[11] Katholieke Univ Leuven, Fac Med, Dept Neurosci, Leuven, Belgium

关键词: Frontotemporal dementia;    FTD;    Amyotrophic lateral sclerosis;    ALS;    C9orf72;    Modifier;   

DOI  :  10.1016/j.neurobiolaging.2020.07.021

来源: Elsevier

【 摘 要 】

We investigated the impact of the recently described chromosome 6 open reading frame 10 (C6orf10)/LOC101929163 locus as age-at-onset modifier in an extended cohort of Belgian chromosome 9 open reading frame 72 (C9orf72) G4C2 repeat expansion carriers. We genotyped the tagging CpG single-nucleotide polymorphism rs9357140 in 224 confirmed C9orf72 repeat expansion carriers, 102 index cases and 122 relatives, and tested association with onset age. The C9orf72 repeat expansion cohort consisted of 131 symptomatic carriers, that is, 78 with dementia only, 13 with frontotemporal dementia (FTD)-amyotrophic lateral sclerosis (ALS), and 40 ALS only, and 93 presymptomatic carriers. Cox proportional hazard regression analysis failed to identify significant association (adjusted hazard ratio = 1.15, p = 0.3). We further extended our analysis to a Belgian cohort of unrelated, mutation-negative FTD index patients (n = 230), but also found no association (adjusted hazard ratio = 0.96, p = 0.3). Overall, our findings suggest that in the Belgian cohort, the C6orf10/LOC101929163 locus cannot explain the marked variability in age at onset, and other genetic or environmental modifiers must drive the clinical heterogeneity observed among C9orf72 repeat expansion carriers. (C) 2020 The Author(s). Published by Elsevier Inc.

【 授权许可】

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