Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70-74 of the HLA-DRB1 molecule
Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70-74 of the HLA-DRB1 molecule
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DOI：
10.1016/j.jhep.2007.08.019
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发表时间：
2008-01-01
影响因子：
25.7
通讯作者：
Suh, Dong Jin
中科院分区：
文献类型：
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作者：
Lim, Young-Suk;Oh, Heung-Bum;Suh, Dong Jin
背景/目的：发展自身免疫性肝炎（AIH）的风险已被认为与HLA-DRB 1等位基因的存在相关，该等位基因编码DR β的第三高变区（HVR 3）中氨基酸位置67-72处的“共享表位”。我们的目的是确定特定的HLA等位基因是易感1型AIH在韩国人，并验证在这个单一的种族group.Methods：62例确诊为I型AIH和154名健康对照组的共享表位假说。结果：经高分辨分析，AIH患者中DRB 1 0 4 0 5和DQB 1 0 4 0 1等位基因频率明显增高（P = 0 1，OR = 3 74; P = 0 6，OR = 3 95）。由DR β多肽的第67-72位的单字母代码LLEQRR或LLEQKR表示的六个氨基酸基序不足以显示该疾病的风险增加。结论：HLA-DR β 70 - 74位氨基酸序列可能是预测Ⅰ型AM易感性的共同表位假说。(c)2007年由Elsevier B. V.代表欧洲肝脏研究协会发表。
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 DR beta. 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 I 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 DR beta 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-DR beta in order to better predict the susceptibility to type I AM. (c) 2007 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.