HLA-A*02、A*24基因多态性与中国汉族人群HIV-1易感性的关系

The relationship between gene polymorphism of HLA-A*02, A*24 and HIV-1 susceptibility of Chinese Han population

目的探索中国汉族人群人类白细胞抗原HLA-A、B、DR基因多态性与HIV-1易感性之间的关系。方法应用序列特异引物PCR法对HIV-1高暴露不感染人群、健康对照人群和HIV-1感染人群进行HLA分型,分析HLA基因多态性位点在两组或三组人群之间分布的差异。结果三组人群HLA-A、B、DR基因多态性位点中A*03和B*55的分布差异有统计学意义(P<0.05),但这两个位点为低丰度位点。健康对照人群HLA基因型的分析发现,HLA-A*02和A*24基因型在CD8+T细胞HLA-DR表达高低两组的分布差异有统计学意义(P=0.020,0.038),等位基因分析也验证了该位点突变的意义(P=0.007,0.009)。A*02多态性变异与CD8+T细胞HLA-DR表达有显著性负相关(r=-0.257,P=0.008),该位点基因突变与CD8+T细胞HLA-DR的低表达密切相关;A*24多态性变异与HLA-DR在CD8阳性细胞表面的表达有显著性正相关(r=0.195,P=0.045),该位点基因突变与CD8+T细胞HLA-DR的高表达密切相关。结论 HLA-A*02基因多态性变异可能是中国汉族人群HIV-1感染的保护性因素,而HLA-A*24基因多态性变异可能是感染的危险因素。

Objective We explored the relationship between gene polymorphism of HLA- A, B, DR and HIV- 1susceptibility of Chinese Han population. Methods PCR of sequence-specific primers（PCR-SSP） was used to analyze HLAgene polymorphism of highly exposed but persistently seronegative population（HEPS）, healthy controls and HIV- 1 carriers,then the difference of genotype distribution between the two or three populations was analyzed. Results Among all the genepolymorphism site of HLA-A, B, DR, only A＊03 and B＊55 genotype distribution had statistic significance in the above threepopulations（P〈0.05）, but they were all low abundance site. In healthy controls, A＊02 and A＊24 genotype distribution hadsignificant difference between CD8^＋T cell HLA-DR low and high expression groups（P=0.020, 0.038）. The analysis of alleledistribution also confirmed the above results of the difference between the two gene polymorphism（P=0.007, 0.009）. Thedistribution of A＊02 allele showed significant negative correlation with CD8^＋T cell HLA-DR expression（r =-0.257, P=0.008）, the genetic variation of A＊02 had significant correlation with lower expression of CD8^＋T cell HLA-DR, whereas thedistribution of A＊24 displayed a significant positive correlation with CD8^＋T cell HLA-DR expression（r =0.195, P=0.045）,the genetic variation of A＊24 had significant correlation with higher expression of CD8^＋T cell HLA-DR. Conclusion ToChinese Han population, HLA- A＊02 polymorphism mutation may be the protect factor of HIV- 1 infection and HLA- A＊24polymorphism mutation may be the risk factor of HIV-1 infection.