HBV阳性肝癌患者中KIR/HLA-Ⅰ基因多态性的关联研究

Association of KIR/HLA-Ⅰ Gene Polymorphisms in HBV Positive Hepatocellular Carcinoma Patients

目的探讨杀伤细胞免疫球蛋白(KIR)及其配体人类白细胞抗原(HLA)基因的遗传多态性在发生乙肝病毒(HBV)相关性肝癌中的可能作用。方法回顾性分析56例HBV相关性HCC患者与503例健康志愿者的KIR和HLA基因型,探讨KIR基因型、KIR组合型以及KIR-HLA组合型与发生HBV相关性肝癌的相关性。结果比较分析发现,HCC组和对照组KIR基因频率之间的差异无统计学意义(P>0.05)。KIR与其配体HLA-Ⅰ的比较分析中发现,HCC组Bw4频率显著低于对照组(HCC vs control=53.6%vs 66.7%,P=0.05); HCC组2DL2/3+HLA-C1与3DL1+HLA-B Bw4通路的频率显著低于对照组(HCC vs control=67.8%vs 96.0%,P=0.00&HCC vs control=50.0%vs 64.2%,P=0.042)。对KIR基因与HBV-DNA载量关系的调查发现,高载量组中2DS5基因频率均显著高于中载量组和低载量组(High vs Middle=55.6%vs 14.3%,P=0.014&High vs Low 55.6%vs 19.2%,P=0.025)。结论 HCC组中表达KIR-AB3组合型、减少2DL2/3+HLA-C1与3DL1+HLA-B Bw4通路和表达KIR2DS5与NK细胞天然杀伤功能抑制相关联,可能导致HBV感染后高病毒复制能力和不良预后。

Objective To explore the role of genetic polymorphisms of killer cell immunoglobulin （KIR） and its ligandhuman leukocyte antigen （HLA） genes in the occurrence of HBV related liver cancer. Methods The KIR and HLA genotypes of56 HBV related HCC patients and 503 healthy volunteers were retrospectively analyzed, and the correlations of the KIR genotypes, KIR combination type and the KIR-HLA combination type with HBV related liver cancer were investigated. Results Therewas no significant difference in the frequency of KIR genes between the HCC group and the control group （P〉0. 05）. The comparison of KIR and its ligand HLA-玉 showed that the frequency of Bw4 in HCC group was significantly lower than that of thecontrol group （HCC vs control = 53. 6% vs 66. 7%, P= 0. 05）, and the frequency of 2DL2 / 3＋HLA-C1 and 3DL1＋HLA-B Bw4pathway in HCC group was significantly lower than that in the control group （HCC vs control = 67. 8% vs 96. 0%,P = 0. 00 ＆HCC vs control = 50. 0% vs 64. 2%,P = 0. 042）. The investigation of the relationships between KIR genes and the HBV-DNAload showed that the 2DS5 gene frequency in the high load group was significantly higher than that of the medium load group andthe low load group （High vs Middle = 55. 6% vs 14. 3%, P= 0. 014 ＆ High vs Low 55. 6% vs 19. 2%,P= 0. 025）. ConclusionThe expression of KIR -AB3 combination in the HCC group, the reduction of the 2DL2 / 3＋HLA-C1 and 3DL1＋HLA-B Bw4pathway and the expression of KIR2DS5 are associated with the inhibition of the function of NK cells as a natural killer, whichmay lead to the high replication and poor prognosis of the virus after HBV infection.