Higashi Y, Kamikawaji N, Suko H, Ando M
Department of Gastroenterology, Saiseikai Kumamoto Hospital, Japan.
J Gastroenterol Hepatol. 1996 Mar;11(3):241-6. doi: 10.1111/j.1440-1746.1996.tb00069.x.
Hepatitis C virus (HCV) leads to chronic liver disease in at least 50-60% of infected people and approximately 40-50% of these patients will go on to develop cirrhosis due to chronic hepatitis C (HCV-C). The pathogenic mechanisms that result in HCV-C are unknown. Sixty Japanese patients with HCV-C were examined for HLA-A, B, C and DR alleles by serologic typing and for HLA-DQB1 alleles by DNA typing using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. As the control population, 293 healthy un-related Japanese were used. The frequencies of HLA-B61, C(omega)3, DR4, DQB10401 and DQB10402 were increased, while those of HLA-DR9, DQB10301 and DQB10303 were decreased in the patients. The co-ordinate increase in the frequency of HLA-DR4, DQB10401 or 0402 and decrease in the frequency of DR9 or DQB10303 were suggestive of a strong linkage disequilibrium between HLA-DR4 and DQB10401 or 0402 and between HLA-DR9 and DQB10303, respectively. From the odds ratio (OR) analysis, the combinations of HLA-C(omega)3+ DR4-DQB10401 or 0402, or HLA-B61 + DR4 - DQB10401 or 0402 increased the risk for developing HCV-C when compared to each HLA allele alone. This suggested an additive effect for these classes I and II HLA allele combinations in HCV-C. In contrast, HLA-DR9-DQB10303 and DQB10301 may confer resistance to this disease. These results suggest the existence of HLA-linked susceptibility genes to HCV-C.
丙型肝炎病毒（HCV）可导致至少50%至60%的感染者罹患慢性肝病，其中约40%至50%的患者会因慢性丙型肝炎（HCV-C）发展为肝硬化。导致HCV-C的致病机制尚不清楚。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，通过血清学分型对60例日本HCV-C患者进行HLA-A、B、C和DR等位基因检测，采用DNA分型对HLA-DQB1等位基因进行检测。以293名健康无血缘关系的日本人为对照人群。患者中HLA-B61、C(omega)3、DR4、DQB10401和DQB10402的频率升高，而HLA-DR9、DQB10301和DQB10303的频率降低。HLA-DR4、DQB10401或0402频率的协同增加以及DR9或DQB10303频率的降低分别提示HLA-DR4与DQB10401或0402之间以及HLA-DR9与DQB10303之间存在强连锁不平衡。通过优势比（OR）分析，与单独的每个HLA等位基因相比，HLA-C(omega)3 + DR4 - DQB10401或0402，或HLA-B61 + DR4 - DQB10401或0402的组合增加了发生HCV-C的风险。这表明这些I类和II类HLA等位基因组合在HCV-C中具有累加效应。相比之下，HLA-DR9 - DQB10303和DQB10301可能赋予对该疾病的抵抗力。这些结果提示存在与HLA相关的HCV-C易感基因。
