人类白细胞抗原DRB基因多态性与支气管哮喘易感性的相关性研究

目的 探讨人类白细胞抗原－ＤＲＢ基因型在北京地区支气管哮喘患者中的分布。方法 采用序列特异怀引物聚合酶链反应研究了ＨＬＡ－ＤＲＢ的等位基因在５０例哮喘患者和８０例健康者间的分布;放射变应原吸附试验荧光酶标法（ＲＡＳＴ）测定了哮喘患者的总ＩｇＥ（ＴＩｇＥ）,户尘螨特异性ＩｇＥ（ｄｌｓｇＥ）;乙酰甲胆碱支握管激发试验。结果ＨＬＡ－ＤＲ６（１３）基因频率在哮喘组（１７％）明显高于对照组（４．３％）;Ｄ５

HLA-DRB alleles polymorphism in susceptibility to asthma in Beijing Chinese

OBJECTIVES: To investigate whether susceptibility or resistance to asthma associated with HLA-DRB alleles and analyze the relationship between HLA-DRB genes and clinical phenotype of asthma (TIgE, sIgE, BHR). METHODS: Using PCR-SSP(sequence-specific primer polymerase chain reaction), we tested the frequency distribution of HLA-DRB alleles in 50 asthmatic patients and 80 healthy volunteers from Beijing China. All patients had their serum TIgE, IgE antibody specific to house dust mite measured by RAST, bronchial responsiveness assessed by methacholine bronch-provocation (if FEV1% > or = 70%), and broncho-dilation measurement by inhaling salbutamol. RESULTS: There was significantly increased gene frequency of alleles DR6(13), DR52 in asthmatics compared with normal controls (17% vs 4.3%, P < 0.01; 50% vs 17.5%, P < 0.01), and RR was 7.55 and 4.7 respectively. The frequency of DR2(15), DR51 was lower in asthmatics than in controls (7% vs 18% P < 0.01; 2% vs 33.8% P < 0.01). The percentage of HLA haplotype DR6(13)-DR52 was higher in asthmatics than in healthy volunteers (20% vs 4%, P < 0.01, RR 6.4). 70% of individuals sharing DR6(13) gene and 56% of subjects carrying DR52 gene had elevated serum d1 sIgE antibody (> or = +4). There was no relationship between HLA-DRB alleles and total IgE, BHR. CONCLUSIONS: Alleles DR6(13), DR52 are significantly implicated in their susceptibility to asthma, at least they may be closely associated with this disorder. Conversely DR2(15), DR51 alleles might confer protection against asthma. Positive associations between DR6(13), DR52 and IgE response to d1 allergen are noted. HLA-DRB genes are particularly involved in regulating human atopic immune response.