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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 To explore the relationship between human leukocyte antigen HLA-A, B, DR polymorphisms and HIV-1 susceptibility in Chinese Han population. Methods HLA-1 genotypes were detected by polymerase chain reaction-sequence-specific PCR in HIV-1 noninfected, healthy controls and HIV-1 infected individuals. HLA genotypes were analyzed in two or three groups difference. Results The distribution of A * 03 and B * 55 in HLA-A, B and DR polymorphism sites in three groups of patients was significantly different (P <0.05), but the two sites were low abundance sites . HLA-A * 02 and A * 24 genotypes of HLA-DR in CD8 + T cells showed significant difference (P = 0.020,0.038), allele Gene analysis also confirmed the significance of the site mutation (P = 0.007,0.009). There was a significant negative correlation between A * 02 polymorphism and HLA-DR expression of CD8 + T cells (r = -0.257, P = 0.008). The mutation of this site was closely related to the low expression of HLA-DR in CD8 + T cells (R = 0.195, P = 0.045). The mutation of A * 24 was positively correlated with the expression of HLA-DR on the surface of CD8 positive cells (r = 0.195, P = 0.045) closely related. Conclusion The polymorphism of HLA-A * 02 gene may be a protective factor of HIV-1 infection in Chinese Han population, while the variation of HLA-A * 24 gene polymorphism may be a risk factor for infection.