中国华南地区慢性乙型肝炎患者HLA-A等位基因分布的初步调查及其意义  

Investigation of the distribution of different major HLA-A alleles in patients with chronic hepatitis B in Southern China regions

作　　者：梁敏锋[1] 马世武[1] 于乐成[1] 武大林[2] 王战会[1] 侯金林[1] 

机构地区：[1]南方医科大学南方医院肝病中心及感染内科,广州市510515 [2]南方医科大学南方医院组织配型中心,广州市510515

出　　处：《肝脏》2007年第4期240-243,共4页Chinese Hepatology

基　　金：国家自然科学基金资助课题(No.30471549;30571662);中国博士后科学基金一等资助课题(No.2004036019)

摘　　要：目的了解中国华南地区慢性乙型肝炎(CHB)患者HLA-A11、A2、A24、A33等位基因的分布状况,并为筛选HBV特异性CTL新表位提供必要背景资料。方法以267例CHB患者和300例健康献血员为研究对象,提取其外周血染色体基因组DNA,用PCR-SSP法进行HLA-A11、A2、A24、A33等位基因检测型,并进行统计学比较。结果CHB组HLA-A11、A2、A24、A33的基因频率分别为57%、41%、21%、7%,以HLA-A11最常见,较HLA-A2的基因频率高16%。健康对照组四种HLA-A等位基因的频率分别为57%、46%、24%、14%,HLA-A11较HLA-A2的频率高11%。HLA-A33的频率在两组间有显著差异(χ2=7.556,P=0.006)。CHB组HLA-A2/A11、A2/A24、A2/A33、A11/A24、A11/A33、A24/A33的基因频率分别为17%、4%、1%、16%、4%、0.4%,健康人群则为18%、8%、4%、11%、5%、1%,各种基因组合的出现率在两组间近似。HBeAg(+)与HBeAg(-)CHB组比较,HLA-A11(χ2=3.324,P=0.072)、A2(χ2=0.324,P=0.569)、A24(χ2=0.308,P=0.579)、A33(χ2=1.159,P=0.282)等位基因的频率分布在两组间无显著性差异。结论中国华南地区CHB患者和健康人群的主要HLA-A等位基因均为HLA-A11、A2、A24及A33,以HLA-A11最为多见,提示鉴定HLA-A11限制性HBV特异性CTL新表位具有十分重要的意义;此四种等位基因及其组合模式与CHB患者的HBeAg状态无明显相关,但与HBV感染的其他临床特点及抗病毒治疗应答之间的关系有待研究。Objective To investigate the distribution of HLA-All, A2, A24, and A33 alleles in chronic hepatitis B virus （CHB） patients in Southern China, and to provide background information for the screening of new HBV CTL epitopes. Methods Chromosomal genomic DNA specimen extracted from peripheral blood of 267 patients and 300 healthy donors were obtained for HLA-A genotyping with PCR-SSP assays, and the data were analysed with SPSS10.0 software. Results The results of that the frequency of HLA-A11, A2, A24 and A33 alleles was 57 % , 41%, 21% and 7 %, respectively in CHB patients in Southern China, and the most common allele is HLA-A11 which is about 16% more than that of HLA-A2. The frequency of these four alleles in healthy donors was 57%, 46%, 24% and 14% respectively, and HLA-All is about 11% more than that of HLA-A2. Only the distribution of HLA-A33 between the two groups had signifiacant difference. The combination of HLA-A2/A11, A2/A24, A2/A33, A11/A24, A11/A33 or A24/ A33 alleles was 17%, 4%, 1%, 16%, 4%, 0.4% in CHB patients, and 18%, 8%, 4%, 11%, 5%, 1% in healthy donors respectively; there was no significant difference between the two groups. The distribution of HLA-All, A2, A24 and A33 alleles was similar between HBeAg-pesitive and HBeAg-negative CHB patients. Conclusion HLA-A11, A2, A24 and A33 are the major HLA-A alleles in CHB patients of Southern China, of them the most common one is HLA-A11. The importance for identification of HLA-A11- restricted and HBV-specific new CTL epitopes is no less than that of HLA-A2-restricted HBV-specific CTL epitopes for the research of basic and clinical immunology of HBV infection. The distribution of these four major HLA-A alleles and their combination patterns have no significant differences between HBeAg-positive and HBeAg-negative CHB patients, but their influence on clinical features and the response of antiviral therapies in CHB patients should be further investigated.

关 键 词：慢性乙型肝炎 HLA-A PCR-SSP CTL表位 

分 类 号：R512.6[医药卫生—内科学]