摘要：
Objective To study the relationship between HLA allele frequencies in peripheral blood mononuclear cells (PBMCs) and the susceptibility to tuberculosis in southern Chinese population. Methods The polymorphisms of HLA-A and HLA-DRB1 loci in the PBMCs were analyzed in 294 patients with active tuberculosis using polymerase chain reaction-sequence based typing (PCT-SBT). The allele frequencies in the patients were compared with the data from 644 control southern Chinese subjects obtained from the online database Allele Frequencies in Worldwide Population. Results The frequencies of HLA-A*0101 and HLA-DRB1*1454 alleles in the patient cohort with pulmonary tuberculosis were significantly higher than those in the control group (2.4％vs 0.6％,χ2=10.788, P=0.001, Pc=0.016;7.5％vs 0％,χ2=69.850, P<0.0001);the frequencies of HLA-DRB1*1202 and HLA-DRB1*1401 alleles were significantly lower in this patient cohort than in the control group (10.4％vs 16.1％,χ2=9.845, P=0.002, Pc=0.044;0％vs 3.1％,χ2=18.520, P<0.001). Conclusion The frequencies of HLA-A and HLA-DRB1 alleles are correlated with the susceptibility to active tuberculosis in this southern Chinese population. HLA-A*0101, HLA-DRB1*1454 and the other 3 alleles are likely susceptible genes to tuberculosis, while HLA-DRB1*1202, HLA-DRB1*1401 and the other 4 alleles can be protective genes in this population.%目的 研究中国南方活动性肺结核患者的HLA-A、HLA-DRB1等位基因频率分布,并分析该地区HLA-A、HLA-DRB1高分辨分型等位基因与肺结核遗传易感性的关联.方法 采用聚合酶链式反应-直接测序基因分型(PCR-SBT),检测中国南方人群活动性肺结核患者(n=294)的HLA-A和HLA-DRB1高分辨等位基因多态性,并与来自HLA频率数据库[(http://www.allelefrequencies.net)]中国南方汉族人群(n=644)的HLA-A和HLA-DRB1等位基因多态性数据进行频率分布比较.结果 活动性肺结核(APTB)病例组中HLA-A*0101和HLA-DRB1*1454基因频率显著高于人群对照组(2.4％vs 0.6％,χ2=10.788,P=0.001,Pc=0.016;7.5％vs 0％,χ2=69.850,P<0.0001);而APTB病例组中HLA-DRB1*1202和HLA-DRB1*1401基因频率显著低于人群对照组(10.4％vs 16.1％,χ2=9.845,P=0.002,Pc=0.044;0％vs 3.1％,χ2=18.520,P<0.0001).结论 在中国南方人群中,结核病的易感性与HLA-A和HLA-DRB1高分辨等位基因有一定的相关性,结果提示HLA-A*0101和HLA-DRB1*1454等可能是中国南方人群的肺结核易感基因,而HLA-DRB1*1202和HLA-DRB1*1401等可能是该地区人群结核病的保护基因.
