Principal contribution of HLA-DQ alleles, DQB1*06:04 and DQB1*03:01, to disease resistance against primary biliary cholangitis in a Japanese population.
Sci Rep
; 7(1): 11093, 2017 09 11.
Article
em En
| MEDLINE
| ID: mdl-28894202
ABSTRACT
Identification of the primary allele(s) in HLA class II associated diseases remains challenging because of a tight linkage between alleles of HLA-DR and -DQ loci. In the present study, we determined the genotypes of seven HLA loci (HLA-A, -B, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) for 1200 Japanese patients with primary biliary cholangitis and 1196 controls. Observation of recombination derivatives facilitated an evaluation of the effects of individual HLA alleles consisting of disease-prone/disease-resistant HLA haplotypes. Consequently, a primary contribution of DQB1*0604 (odds ratio 0.19, p = 1.91 × 10-22), DQB1*0301 (odds ratio 0.50, p = 6.76 × 10-10), DRB1*0803 (odds ratio 1.75, p = 1.01 × 10-7) and DQB1*0401 (odds ratio 1.50, p = 9.20 × 10-6) was suggested. Epistasis of the protective DQB1*0604 to risk conferred by DRB1*0803 was demonstrated by subpopulation analysis, implicating the presence of an active immunological mechanism that alleviates pathogenic autoimmune reactions. Further, the contribution of the aforementioned HLA alleles as well as an HLA-DP allele, DPB1*0201 to the association signals of 304 loci among 4103 SNPs in the HLA region at the genome-wide level of significance (p values less than 5 × 10-8) was demonstrated by the stepwise exclusion of the individuals possessing these HLA alleles from the comparison.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colangite
/
Predisposição Genética para Doença
/
Alelos
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Estudos de Associação Genética
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Resistência à Doença
/
Cadeias beta de HLA-DQ
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão