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http://purl.uniprot.org/citations/29088299http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29088299http://www.w3.org/2000/01/rdf-schema#comment"

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*03:01 and *04:01 are associated with type 1 AIH in European and *04:05 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*04:01 (P = 0.0006, corrected P [Pc] = 0.0193, odds ratio [OR] 2.97, 95% confidence interval [CI] 1.62-5.43), DRB1*04:05 (P = 1.89×10-21, Pc = 5.86×10-20, OR 3.41, 95% CI 2.65-4.38), and DQB1*04:01 (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*13:02 (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*04:05-DQB1*04:01/DRB1*08:02-DQB1*03:02 (P = 0.0004, OR 24.77, 95% CI 1.45-424.31) and DRB1*04:05-DQB1*04:01/DRB1*08:03-DQB1*06:01 (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*04:05 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-β 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."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0187325"xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Abe K."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Hashimoto S."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Ohta H."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Nakamura M."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Nakamura H."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Nagaoka S."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Sakai H."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Yamashita H."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Takahashi A."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Yoshizawa K."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Komori A."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Naganuma A."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Yasunami M."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Oka S."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Furukawa H."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Yatsuhashi H."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Tsuchiya N."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Kawasaki A."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Tohma S."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Ohira H."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Migita K."xsd:string
http://purl.uniprot.org/citations/29088299http://purl.uniprot.org/core/author"Abiru S."xsd:string
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