NDLI: Human Leukocyte Antigen Class II Haplotypes Affect Clinical Characteristics and Progression of Type 1 Autoimmune Hepatitis in Japan

Content Provider	PubMed Central
Author	Umemura, Takeji Katsuyama, Yoshihiko Yoshizawa, Kaname Kimura, Takefumi Joshita, Satoru Komatsu, Michiharu Matsumoto, Akihiro Tanaka, Eiji Ota, Masao
Editor	Re, Valli De
Copyright Year	2014
Abstract	Although we earlier demonstrated that the human leukocyte antigen (HLA) DRB104:05 allele was associated with susceptibility to autoimmune hepatitis (AIH) in Japan, the precise relationship of HLA haplotype and the role of amino acid alignment with disease susceptibility and progression has not been fully clarified. We reinvestigated HLA class I A, B, and C and HLA class II DRB1, DQB1, and DPB1 alleles and haplotypes in a larger new cohort of 156 Japanese patients with type 1 AIH and compared them with the published data of 210 healthy subjects. The DRB104:05-DQB104:01 haplotype was significantly associated with AIH susceptibility (30% vs. 11%, P = 1.2×10−10; odds ratio [OR] = 3.51) and correlated with elevated serum IgG (3042 vs. 2606 mg/dL, P = 0.041) and anti-smooth muscle antigen positivity (77% vs. 34%, P = 0.000006). No associations with HLA-DPB1 alleles were found. The HLA A24:02 and C01:02 alleles were associated with disease susceptibility (corrected P = 0.0053 and 0.036, respectively), but this likely constituents of a long ranged haplotype including DRB104:05-DQB104:01 haplotype. Conversely, the DRB115:01-DQB106:02 haplotype was associated with protection from both disease onset (5% vs. 13%, P = 0.00057; OR = 0.38) and the development of hepatocellular carcinoma (25% vs. 5%, P = 0.017; OR = 6.81). The frequency of the DRB108:03-DQB1*06:01 haplotype was significantly higher in patients who developed hepatic failure (22% vs. 6%, P = 0.034; OR = 4.38). In conclusion, this study established the role of HLA haplotypes in determining AIH susceptibility and progression in the Japanese population. Additional sequencing of the entire HLA region is required to more precisely identify the genetic components of AIH.
Related Links	http://dx.doi.org/10.1371/journal.pone.0100565
Starting Page	100565
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	6
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-06-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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Correction: Human Leukocyte Antigen Class II Haplotypes Affect Clinical Characteristics and Progression of Type 1 Autoimmune Hepatitis in Japan

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Correction: Human Leukocyte Antigen Class II Haplotypes Affect Clinical Characteristics and Progression of Type 1 Autoimmune Hepatitis in Japan

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