Kuzushita N, Hayashi N, Moribe T, Katayama K, Kanto T, Nakatani S, Kaneshige T, Tatsumi T, Ito A, Mochizuki K, Sasaki Y, Kasahara A, Hori M
First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
Hepatology. 1998 Jan;27(1):240-4. doi: 10.1002/hep.510270136.
The human leukocyte antigen is a crucial genetic factor that initiates or regulates immune response by presenting foreign or self antigens to T lymphocytes. The aim of this study was to investigate whether HLA polymorphism is associated with the onset or progression of liver injury in chronic hepatitis C virus (HCV) infection. We determined HLA class I antigens and class II alleles in 130 hepatitis C virus (HCV)-infected patients (33 carriers with persistently normal alanine transaminase [ALT] values and 97 patients with chronic liver disease [CLD]). HLA class I (A, B) was typed serologically, and class II (DRB1, DQB1) was typed by means of polymerase chain reaction-restriction fragment length polymorphism methods. The frequencies of DRB10405 and DQB10401 were higher in HCV-infected patients than in uninfected subjects. Among HCV-infected patients, the frequencies of B54, DRB10405, and DQB10401 were significantly higher in patients with CLD than in those carriers with persistently normal ALT values, whereas DRB11302, DRB11101, and DQB10604 were more frequently found in carriers with persistently normal ALT values than in patients with CLD. From extended haplotype analyses, in carriers with B54-DRB10405-DQB10401 haplotype, the risk of having liver injury was 13.2 times greater than in carriers with DRB10405-DQB10401 but without B54 [P = 0.0015, Haldane odds ratio = 13.2 (95% confidence interval, 1.7-103.8)]. In contrast, carriers with B44-DRB11302-DQB10604 had a 12.7-fold lower relative risk of developing liver injury compared to those with the haplotype containing B44 but not DRB11302-DQB10604 [P = 0.0076, Haldane odds ratio = 0.079 (0.009-0.695)]. Our findings show that extended haplotypes including class I B54 are closely associated with the progression of liver injury, whereas extended haplotypes including class II DRB11302-DQB1*0604 are associated with low hepatitis activity in chronic HCV infection.
人类白细胞抗原是一种关键的遗传因素，通过将外来或自身抗原呈递给T淋巴细胞来启动或调节免疫反应。本研究的目的是调查人类白细胞抗原多态性是否与慢性丙型肝炎病毒（HCV）感染中肝损伤的发生或进展相关。我们测定了130例丙型肝炎病毒（HCV）感染患者（33例丙氨酸转氨酶[ALT]值持续正常的携带者和97例慢性肝病[CLD]患者）的HLA I类抗原和II类等位基因。HLA I类（A、B）通过血清学方法分型，II类（DRB1、DQB1）通过聚合酶链反应-限制性片段长度多态性方法分型。HCV感染患者中DRB10405和DQB10401的频率高于未感染的受试者。在HCV感染患者中，CLD患者中B54、DRB10405和DQB10401的频率显著高于ALT值持续正常的携带者，而DRB11302、DRB11101和DQB10604在ALT值持续正常的携带者中比CLD患者中更常见。通过扩展单倍型分析，在具有B54-DRB10405-DQB10401单倍型的携带者中，发生肝损伤的风险比具有DRB10405-DQB10401但无B54的携带者高13.2倍[P = 0.0015，霍尔丹优势比 = 13.2（95%置信区间，1.7 - 103.8）]。相反，与具有包含B44但不包含DRB11302-DQB10604的单倍型的携带者相比，具有B44-DRB11302-DQB10604的携带者发生肝损伤的相对风险低12.7倍[P = 0.0076，霍尔丹优势比 = 0.079（0.009 - 0.695）]。我们的研究结果表明，包括I类B54的扩展单倍型与肝损伤的进展密切相关，而包括II类DRB11302-DQB1*0604的扩展单倍型与慢性HCV感染中的低肝炎活动度相关。
