KIR-HLA基因多态性与散发性急性戊型肝炎的关系

Association between killer cell immunoglobulin- like receptor/human leukocyte antigen gene polymorphisms and sporadic acute hepatitis E

目的探讨杀伤性免疫球蛋白样受体(KIR)及其配体人类白细胞抗原(HLA)的基因多态性与散发性急性戊型肝炎(AHE)的相关性。方法收集2015年8月-2016年9月期间于复旦大学附属公共卫生临床中心肝炎一科住院的AHE患者42例,另招募健康受试者30例作为对照组。提取入组对象外周血基因组DNA,采用序列特异性引物PCR法扩增KIR基因,并利用Sanger测序法对HLA进行基因分型,分析KIR-HLA分布与散发性AHE的关系。计数资料组间比较采用χ~2检验。结果两组均可检测到16种KIR基因(包括抑制型受体基因2DL1-3、2DL5、3DL1-3,激活型受体基因2DS1-5、3DS1,较特殊的抑制型/激活型受体基因2DL4,内参基因DRB1及假基因2DP1),同时HLA-B(包括HLA-Bw4、HLA-Bw6、HLA-Bw4/Bw6)、HLA-C(包括HLA-C1/C1、HLA-C1/C2、HLA-C2/C2)亦可检测。AHE患者中抑制型基因KIR 2DL3/2DL5/3DL2/3DL3出现的频率显著低于对照组(64.3%vs 93.3%,P<0.05;23.8%vs 56.7%,P<0.05;71.4%vs 100%,P<0.05;69.0%vs 100%,P<0.05);AHE患者HLA-C1/C2和3DL1/HLA-Bw4基因的出现频率低于对照组(19.0%vs 40.0%,P<0.05;45.2%vs 73.3%,P<0.05);另外,AHE患者中HLA-C1/C1基因出现的频率高于对照组(71.4%vs 46.7%,P<0.05)。结论抑制型基因KIR 2DL3/2DL5/3DL2/3DL3,HLA-C1/C1、C1/C2和3DL1/HLA-Bw4的基因分布差异可能与HEV感染导致散发性AHE有一定关系。

Objective To investigate the association between killer cell immunoglobulin-like receptor（KIR）/human leukocyte antigen（HLA） gene polymorphisms and sporadic acute hepatitis E（AHE）.Methods A total of 42 AHE patients who were hospitalized in First Department of Hepatitis,Public Health Clinical Center Affiliated to Fudan University,from August 2015 to September 2016 were enrolled,and 30 healthy subjects were enrolled as control group.Genomic DNA was extracted from the peripheral blood,and PCR/sequence specific primer was used for the amplification of KIR gene.Sanger sequencing was used to determine the genotype of HLA,and the association between KIR-HLA distribution and sporadic AHE was analyzed.The chi-square test was used for comparison of categorical data between groups.Results A total of 16 KIR genes were detected in each group,including inhibitory receptor genes 2DL1-3,2DL5,and 3DL1-3,activating receptor genes 2DS1-5 and 3DS1,the special inhibitory/activating receptor gene 2DL4,internal reference gene DRB1,and pseudogene 2DP1,as well as HLA-B（including HLA-Bw4,HLA-Bw6,and HLA-Bw4/Bw6） and HLA-C（including HLA-C1/C1,HLA-C1/C2,and HLA-C2/C2）,were also detected.Compared with the control group,the AHE group had significantly lower frequencies of inhibitory genes KIR 2DL3（64.3% vs 93.3%,P〈0.05）,2DL5（23.8% vs 56.7%,P〈0.05）,3DL2（71.4% vs 100%,P〈0.05）,and 3DL3（69.0% vs 100%,P〈0.05）,significantly lower frequencies of HLA-C1C2（19.0% vs 40.0%,P〈0.05） and 3DL1/HLA-Bw4（45.2% vs 73.3%,P〈0.05）,and a significantly higher frequency of HLA-C1/C1 gene（71.4% vs 46.7%,P〈0.05）.Conclusion The difference in the distribution of inhibitory genes KIR 2DL3,2DL5,3DL2,and 3DL3,HLA-C1C1/C1C2,and 3DL1/HLA-Bw4 may be associated with sporadic AHE caused by hepatitis E virus infection.