Hypomorphic MGAT5 polymorphisms promote multiple sclerosis cooperatively with MGAT1 and interleukin-2 and 7 receptor variants.
J Neuroimmunol
; 256(1-2): 71-6, 2013 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-23351704
ABSTRACT
Deficiency of the Golgi N-glycan branching enzyme Mgat5 in mice promotes T cell hyperactivity, endocytosis of CTLA-4 and autoimmunity, including a spontaneous multiple sclerosis (MS)-like disease. Multiple genetic and environmental MS risk factors lower N-glycan branching in T cells. These include variants in interleukin-2 receptor-α (IL2RA), interleukin-7 receptor-α (IL7RA), and MGAT1, a Golgi branching enzyme upstream of MGAT5, as well as vitamin D3 deficiency and Golgi substrate metabolism. Here we describe linked intronic variants of MGAT5 that are associated with reduced N-glycan branching, CTLA-4 surface expression and MS (p=5.79×10(-9), n=7,741), the latter additive with the MGAT1, IL2RA and IL7RA MS risk variants (p=1.76×10(-9), OR=0.67-1.83, n=3,518).
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Variação Genética
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Receptores de Interleucina-2
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N-Acetilglucosaminiltransferases
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Receptores de Interleucina-7
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Esclerose Múltipla
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neuroimmunol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos