HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype
Publication Date
October 31, 2017
Authors
Shomi Oka, Hiroshi Furukawa, Michio Yasunami, Aya Kawasaki, et al
Volume
12
Issue
10
Pages
e0187325
DOI
https://dx.plos.org/10.1371/journal.pone.0187325
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0187325
Scopus
85032723859
Mendeley
http://www.mendeley.com/research/hladrb1-dqb1-alleles-japanese-type-1-autoimmune-hepatitis-predisposing-role-dr4dr8-heterozygous-geno
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Mendeley | Further Information

{"title"=>"HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype", "type"=>"journal", "authors"=>[{"first_name"=>"Shomi", "last_name"=>"Oka", "scopus_author_id"=>"55208482300"}, {"first_name"=>"Hiroshi", "last_name"=>"Furukawa", "scopus_author_id"=>"55204364500"}, {"first_name"=>"Michio", "last_name"=>"Yasunami", "scopus_author_id"=>"7003417005"}, {"first_name"=>"Aya", "last_name"=>"Kawasaki", "scopus_author_id"=>"7102376050"}, {"first_name"=>"Hitomi", "last_name"=>"Nakamura", "scopus_author_id"=>"55655708900"}, {"first_name"=>"Minoru", "last_name"=>"Nakamura", "scopus_author_id"=>"56389919200"}, {"first_name"=>"Atsumasa", "last_name"=>"Komori", "scopus_author_id"=>"36720543200"}, {"first_name"=>"Seigo", "last_name"=>"Abiru", "scopus_author_id"=>"8636671500"}, {"first_name"=>"Shinya", "last_name"=>"Nagaoka", "scopus_author_id"=>"12139022600"}, {"first_name"=>"Satoru", "last_name"=>"Hashimoto", "scopus_author_id"=>"50161590600"}, {"first_name"=>"Atsushi", "last_name"=>"Naganuma", "scopus_author_id"=>"7004364046"}, {"first_name"=>"Noriaki", "last_name"=>"Naeshiro", "scopus_author_id"=>"57201289896"}, {"first_name"=>"Kaname", "last_name"=>"Yoshizawa", "scopus_author_id"=>"7102117549"}, {"first_name"=>"Haruhiro", "last_name"=>"Yamashita", "scopus_author_id"=>"7403649828"}, {"first_name"=>"Keisuke", "last_name"=>"Ario", "scopus_author_id"=>"10340702600"}, {"first_name"=>"Hajime", "last_name"=>"Ohta", "scopus_author_id"=>"56999719400"}, {"first_name"=>"Hironori", "last_name"=>"Sakai", "scopus_author_id"=>"35350851300"}, {"first_name"=>"Iwao", "last_name"=>"Yabuuchi", "scopus_author_id"=>"57196357084"}, {"first_name"=>"Atsushi", "last_name"=>"Takahashi", "scopus_author_id"=>"35371084400"}, {"first_name"=>"Kazumichi", "last_name"=>"Abe", "scopus_author_id"=>"56506069100"}, {"first_name"=>"Hiroshi", "last_name"=>"Yatsuhashi", "scopus_author_id"=>"7003591362"}, {"first_name"=>"Shigeto", "last_name"=>"Tohma", "scopus_author_id"=>"6701350194"}, {"first_name"=>"Hiromasa", "last_name"=>"Ohira", "scopus_author_id"=>"7005446955"}, {"first_name"=>"Naoyuki", "last_name"=>"Tsuchiya", "scopus_author_id"=>"55265126400"}, {"first_name"=>"Kiyoshi", "last_name"=>"Migita", "scopus_author_id"=>"35420526600"}], "year"=>2017, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"85032723859", "pmid"=>"29088299", "pui"=>"619011416", "isbn"=>"1111111111", "scopus"=>"2-s2.0-85032723859", "doi"=>"10.1371/journal.pone.0187325", "issn"=>"19326203"}, "id"=>"f7e199ee-327b-3af7-88ad-7707886e694f", "abstract"=>"Objective: Autoimmune hepatitis (AIH) is a chronic progressive liver disease. AIH is composed pre- dominantly 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,OR3.41, 95% CI 2.65–4.38), and DQB1*04:01 (P = 4.66×10−18, Pc = 6.99×10−17,OR3.89, 95% CI 2.84–5.33) and the protective association of DRB1*13:02 (P = 0.0003, Pc = 0.0080,OR0.48, 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,OR3.52, 95% CI 2.34–5.29). Susceptible diplo- types were DRB1*04:05-DQB1*04:01/DRB1*08:02-DQB1*03:02 (P = 0.0004,OR24.77, 95% CI 1.45–424.31) and DRB1*04:05-DQB1*04:01/DRB1*08:03-DQB1*06:01 (P = 1.18×10−6,OR10.64, 95% CI 3.19–35.46). Serum levels of ImmunoglobulinGand Immu- noglobulin 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-complementingDQα-β heterodimer molecules encoded by DQA1 allele of one haplotype and the DQB1 allele of the other haplo- type, as it was proposed in the HLA association studies of Type 1 diabetes.", "link"=>"http://www.mendeley.com/research/hladrb1-dqb1-alleles-japanese-type-1-autoimmune-hepatitis-predisposing-role-dr4dr8-heterozygous-geno", "reader_count"=>10, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Researcher"=>1, "Student > Doctoral Student"=>1, "Other"=>2, "Student > Master"=>1, "Professor"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Researcher"=>1, "Student > Doctoral Student"=>1, "Other"=>2, "Student > Master"=>1, "Professor"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Computer Science"=>{"Computer Science"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

Scopus | Further Information

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2019-08-27 21:06:30 UTC
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