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  • Title: Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70-74 of the HLA-DRB1 molecule.
    Author: Lim YS, Oh HB, Choi SE, Kwon OJ, Heo YS, Lee HC, Suh DJ.
    Journal: J Hepatol; 2008 Jan; 48(1):133-9. PubMed ID: 18022727.
    Abstract:
    BACKGROUND/AIMS: The risk of developing autoimmune hepatitis (AIH) has been suggested to be associated with the presence of HLA-DRB1 alleles encoding the 'shared epitope' at amino acid positions 67-72 in the third hypervariable region (HVR3) of DRbeta. We aimed to identify the specific HLA alleles that are susceptible to type 1 AIH in Koreans, and to validate the shared epitope hypothesis in this single ethnic group. METHODS: Sixty-two adult patients with definite type 1 AIH and 154 healthy controls were enrolled. Alleles of HLA class I and II genes were genotyped using sequence-based typing. RESULTS: By high-resolution analysis, the frequencies of DRB1 *0405 and DQB1 *0401 were significantly increased in patients with AIH (P = 0.0001, OR = 3.74; P = 0.00006, OR = 3.95, respectively). The six amino acid motif represented by the single letter code LLEQRR or LLEQKR at positions 67-72 of the DRbeta polypeptide was not sufficient to show an increased risk for the disease. Interestingly, the QRRAA motif at positions 70-74 was significantly increased in Korean patients (P=0.04, OR=1.84). CONCLUSIONS: The shared epitope hypothesis may be extended to the amino acid motif at positions 70-74 of HLA-DRbeta in order to better predict the susceptibility to type 1 AIH.
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