Human leukocyte antigen class II haplotypes affect clinical characteristics and progression of type 1 autoimmune hepatitis in Japan.
Human leukocyte antigen class II haplotypes affect clinical characteristics and progression of type 1 autoimmune hepatitis in Japan.
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DOI：
10.1371/journal.pone.0100565
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ota M
中科院分区：
文献类型：
--
作者：
Umemura T;Katsuyama Y;Yoshizawa K;Kimura T;Joshita S;Komatsu M;Matsumoto A;Tanaka E;Ota M
尽管我们早先证实人类白细胞抗原(HLADRB1)DRB1*04：05等位基因与日本自身免疫性肝炎(AIH)的易感性相关，但人类白细胞抗原(HLADRB1*04：05)单倍型和氨基酸序列与疾病易感性和疾病进展的确切关系尚未完全阐明。我们重新调查了156例日本1型AIH患者的新队列中的人类白细胞抗原I类A、B、C类和人类白细胞抗原II类DRB1、DQB1和DPB1等位基因和单倍型，并与已发表的210名健康受试者的数据进行了比较。DRB1*04：05-DQB1*04：01单倍型与AIH易感性显著相关(30%比11%，P = 1.2×10−10；优势比[OR] = 3.51)，并与血清免疫球蛋白升高(3042比2606 mg/dL，P = 0.041)和抗平滑肌抗原阳性(77%比34%，P = 0.000006)相关。未发现与人类白细胞抗原-DPB1等位基因相关。HLAA*24：02和C*01：02等位基因与疾病易感性相关(校正P = 分别为0.0053和0.036)，但这可能是包括DRB1*04：05-DQB1*04：01单倍型的长距离单倍型成分。相反，DRB1*15：01-DQB1*06：02单倍型与预防疾病(5%比13%，P = 0.00057；OR = 0.38)和肝细胞癌的发生(25%比5%，P = 0.017；OR = 6.81)相关。DRB1*08：03-DQB1*06：01单倍型频率在发生肝功能衰竭的患者中显著升高(22%vs.6%，P = 0.034；OR = 4.38)。总之，这项研究确定了人类白细胞抗原单倍型在确定日本人群中AIH的易感性和进展中的作用。为了更准确地识别AIH的遗传成分，需要对整个人类白细胞抗原区域进行额外的测序。
Although we earlier demonstrated that the human leukocyte antigen (HLA) DRB1*04:05 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 DRB1*04:05-DQB1*04:01 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 A*24:02 and C*01:02 alleles were associated with disease susceptibility (corrected P = 0.0053 and 0.036, respectively), but this likely constituents of a long ranged haplotype including DRB1*04:05-DQB1*04:01 haplotype. Conversely, the DRB1*15:01-DQB1*06:02 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 DRB1*08:03-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.
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