Multiple sclerosis susceptibility loci do not alter clinical and MRI outcomes in clinically isolated syndrome

被引：16

作者：

Kalincik, T. ^{[1
,2
,3
,4
,5
,6
,7
]}

Guttmann, C. R. G. ^{[8
,9
]}

Krasensky, J. ^{[3
,10
]}

Vaneckova, M. ^{[3
,10
]}

Lelkova, P. ^{[3
,11
]}

Tyblova, M. ^{[1
,2
,3
]}

Seidl, Z. ^{[3
,10
]}

De Jager, P. L. ^{[4
,12
]}

Havrdova, E. ^{[1
,2
,3
]}

Horakova, D. ^{[1
,2
,3
]}

机构：

[1] Charles Univ Prague, Fac Med 1, Dept Neurol, Prague, Czech Republic

[2] Charles Univ Prague, Fac Med 1, Ctr Clin Neurosci, Prague, Czech Republic

[3] Gen Univ Hosp Prague, Prague, Czech Republic

[4] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA

[5] Univ Melbourne, Dept Med, Melbourne Brain Ctr, Melbourne, Vic, Australia

[6] Univ Melbourne, Dept Neurol, Melbourne Brain Ctr, Melbourne, Vic, Australia

[7] Royal Melbourne Hosp, Melbourne, Vic, Australia

[8] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Ctr Neurol Imaging, Boston, MA 02115 USA

[9] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Neurol Imaging, Boston, MA 02115 USA

[10] Charles Univ Prague, Fac Med 1, Dept Radiol, Prague, Czech Republic

[11] Charles Univ Prague, Fac Med 1, Dept Pediat, Prague, Czech Republic

[12] Harvard Univ, Sch Med, Boston, MA USA

来源：

GENES AND IMMUNITY | 2013年 / 14卷 / 04期

关键词：

multiple sclerosis; susceptibility; prognosis; genotype; phenotype; MRI; HLA-DR; AGE; HLA-DR2; ALLELES; AZATHIOPRINE; PROGRESSION; INTERFERON; DIAGNOSIS; PHENOTYPE; SEVERITY;

D O I：

10.1038/gene.2013.17

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

It has not yet been established whether genetic predictors of multiple sclerosis (MS) susceptibility also influence disease severity and accumulation of disability. Our aim was to evaluate associations between 16 previously validated genetic susceptibility markers and MS phenotype. Patients with clinically isolated syndrome verified by positive magnetic resonance imaging (MRI) and cerebrospinal fluid findings (n = 179) were treated with interferon-beta. Disability and volumetric MRI parameters were evaluated regularly for 2 years. Sixteen single-nucleotide polymorphisms (SNPs) previously validated as predictors of MS susceptibility in our cohort and their combined weighted genetic risk score (wGRS) were tested for associations with clinical (conversion to MS, relapses and disability) and MRI disease outcomes (whole brain, grey matter and white matter volumes, corpus callosum cross-sectional area, brain parenchymal fraction, T2 and T1 lesion volumes) 2 years from disease onset using mixed-effect models. We have found no associations between the tested SNPs and the clinical or MRI outcomes. Neither the combined wGRS predicted MS activity and progression over 2-year follow-up period. Power analyses confirmed 90% power to identify clinically relevant changes in all outcome variables. We conclude that the most important MS susceptibility loci do not determine MS phenotype and disease outcomes.

引用

页码：244 / 248

页数：5

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