Genetic risk factors for pediatric-onset multiple sclerosis.
Mult Scler
; 24(14): 1825-1834, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-28980494
ABSTRACT
BACKGROUND:
Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology.OBJECTIVE:
We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS.METHODS:
Cases with onset <18 years (n = 569) and controls (n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases (n = 7588).RESULTS:
HLA-DRB1*1501 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10-16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated (p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval 2.33, 3.32, p < 2.0 × 10-16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA-DRB1*1501 and HLA-A*02.CONCLUSION:
Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA-DRB1*1501 and HLA-A*02 are also associated with POMS.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
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Polimorfismo de Nucleotídeo Único
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Cadeias HLA-DRB1
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Esclerose Múltipla
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article