HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype.
PLoS One
; 12(10): e0187325, 2017.
Article
de En
| MEDLINE
| ID: mdl-29088299
ABSTRACT
OBJECTIVE:
Autoimmune hepatitis (AIH) is a chronic progressive liver disease. AIH is composed predominantly of type 1 in Japanese populations. The genetic and environmental factors are associated with the pathogenesis of AIH. HLA-DRB1*0301 and *0401 are associated with type 1 AIH in European and *0405 in Japanese populations. Here, we conducted an HLA association study in order to find HLA alleles or haplotypes predisposing or protective for Japanese AIH.METHODS:
HLA-DRB1 and DQB1 genotyping of 360 type 1 AIH patients and 1026 healthy controls was performed.RESULTS:
The predisposing association of DRB1*0401 (P = 0.0006, corrected P [Pc] = 0.0193, odds ratio [OR] 2.97, 95% confidence interval [CI] 1.62-5.43), DRB1*0405 (P = 1.89×10-21, Pc = 5.86×10-20, OR 3.41, 95% CI 2.65-4.38), and DQB1*0401 (P = 4.66×10-18, Pc = 6.99×10-17, OR 3.89, 95% CI 2.84-5.33) and the protective association of DRB1*1302 (P = 0.0003, Pc = 0.0080, OR 0.48, 95% CI 0.32-0.72) with Japanese type 1 AIH were observed. An association of the DR4/DR8 heterozygous genotype with Japanese AIH was identified for the first time (P = 3.12×10-9, OR 3.52, 95% CI 2.34-5.29). Susceptible diplotypes were DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 (P = 0.0004, OR 24.77, 95% CI 1.45-424.31) and DRB1*0405-DQB1*0401/DRB1*0803-DQB1*0601 (P = 1.18×10-6, OR 10.64, 95% CI 3.19-35.46). Serum levels of Immunoglobulin G and Immunoglobulin M, International Autoimmune Hepatitis Group score, positive rate of anti-smooth muscle antibodies, and the rate of definite AIH were higher in AIH patients with DRB1*0405 than without.CONCLUSIONS:
The important roles of specific combinations of DRB1 and DQB1 alleles or haplotypes in the pathogenesis of type 1 AIH were suggested. The association of DR4/DR8 heterozygous genotype suggested the pathologic importance of trans-complementing DQα-ß heterodimer molecules encoded by DQA1 allele of one haplotype and the DQB1 allele of the other haplotype, as it was proposed in the HLA association studies of Type 1 diabetes.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Hépatite auto-immune
/
Prédisposition génétique à une maladie
/
Allèles
/
Chaines bêta des antigènes HLA-DQ
/
Chaines HLA-DRB1
/
Génotype
/
Hétérozygote
Type d'étude:
Prognostic_studies
Limites:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
PLoS One
Sujet du journal:
CIENCIA
/
MEDICINA
Année:
2017
Type de document:
Article
Pays d'affiliation:
Japon
Pays de publication:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA