Source
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
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.