Seki T, Kiyosawa K, Ota M, Furuta S, Fukushima H, Tanaka E, Yoshizawa K, Kumagai T, Mizuki N, Ando A
Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Hepatology. 1993 Jul;18(1):73-8.
To investigate the relationship between distribution of human leukocyte antigen alleles and susceptibility to primary biliary cirrhosis among Japanese, we performed serological typing and human leukocyte antigen DP genotyping in 47 Japanese patients with primary biliary cirrhosis. Serologically, the frequency of human leukocyte antigen DQ3 was significantly higher in the patients than in healthy controls, whereas frequency of DR52 was significantly lower in the patients. Human leukocyte antigen DP genotyping using the polymerase chain reaction-restriction-fragment-length polymorphism method showed that the frequency of human leukocyte antigen DPB10501 (85.1%) was significantly higher in patients than in healthy controls but that the frequency of DPB10402 was significantly lower in patients. The positive association of human leukocyte antigen DPB10501 with primary biliary cirrhosis was stronger than that of serological human leukocyte antigen DQ3, which can be explained by its linkage to DPB10501. In addition, three of seven DPB10501-negative patients had DPB10202, suggesting that the human leukocyte antigen DPB1 amino-acid chain plays an important role in the immunogenesis of primary biliary cirrhosis among Japanese patients. Comparative analysis of amino acid sequences from DPB1 alleles indicated that a Leu at position 35 of the DPB1 chain likely contributes to the susceptibility to primary biliary cirrhosis among the Japanese.
为了研究日本人群中人类白细胞抗原等位基因分布与原发性胆汁性肝硬化易感性之间的关系，我们对47例日本原发性胆汁性肝硬化患者进行了血清学分型和人类白细胞抗原DP基因分型。血清学检测显示，患者中人类白细胞抗原DQ3的频率显著高于健康对照，而DR52的频率则显著低于健康对照。采用聚合酶链反应-限制性片段长度多态性方法进行人类白细胞抗原DP基因分型，结果显示患者中人类白细胞抗原DPB10501（85.1%）的频率显著高于健康对照，但DPB10402的频率则显著低于健康对照。人类白细胞抗原DPB10501与原发性胆汁性肝硬化的正相关性强于血清学人类白细胞抗原DQ3，这可以通过其与DPB10501的连锁关系来解释。此外，7例DPB10501阴性患者中有3例携带DPB10202，提示人类白细胞抗原DPB1氨基酸链在日本患者原发性胆汁性肝硬化的免疫发生中起重要作用。对DPB1等位基因氨基酸序列的比较分析表明，DPB1链第35位的亮氨酸可能与日本人原发性胆汁性肝硬化的易感性有关。
