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J Hepatol. 2005 Apr;42(4):578-84. Epub 2005 Jan 21.

Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis.

Author information

1
Department of Medicine, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Japan. kanamey@hsp.md.shinshu-u.ac.jp

Abstract

BACKGROUND/AIMS:

Genetic predisposition to type 1 autoimmune hepatitis (AIH) is linked mainly to HLA-class II genes. The aim of this study is to scan the HLA region for additional genes which may contribute to type 1 AIH susceptibility.

METHODS:

We performed association analysis using HLA class I and II alleles and 18 polymorphic microsatellite markers distributed throughout the HLA region. We specifically assessed tumor necrosis factor (TNF)-alpha gene polymorphisms.

RESULTS:

The frequencies of HLA-DRB1*0405, DRB4 and DQB1*0401 alleles were significantly higher in AIH patients. The association study revealed the presence of three segments in the HLA region showing significantly low P (Pc) values. The first segment was located around the HLA-DR/-DQ subregion, the second was around the HLA-B54 allele, and the third was around two microsatellites near the TNF gene cluster. However, stratification analysis for the effect of DRB1*0405 eliminated association of the latter two segments. Haplotype D of the TNF-alpha promoter gene polymorphisms was weakly associated with susceptibility, but was found to be not significant after stratification analysis.

CONCLUSIONS:

The most influential gene on type 1 AIH pathogenesis in Japanese is the HLA-DRB1. Other genes in the HLA region, including TNF-alpha, have little or no association with type 1 AIH susceptibility.

PMID:
15763345
DOI:
10.1016/j.jhep.2004.12.019
[Indexed for MEDLINE]
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