中国北方汉族人群人类白细胞抗原-DQA1, -DQB1基因多态性与支气管哮喘遗传易感性的关系

目的：探讨人类白细胞抗原（HLA0－DQA1－DQB1基因多态性与我国北方汉族支气管哮喘患者的相关及连锁关系。方法：采用引物序列特异性聚合酶链反应的方法检测了125例无血缘关系的长期居住在北京及其附近地区的汉族哮喘患者和12个哮喘家系成员183例及96名健康个体HLA－DQA1,－DQB1基因型;用放射变应原吸附法测定哮喘患者血清总IgE(TigE),常见过敏原特异性IgE(户尘螨d1,粉尘螨d2),并进行了哮喘患者支气管舒张试验,乙酰甲胆碱（Mch)气道激发试验。结果：HLA－DQA1＊0104基因和HLA－DAB1＊0201基因在哮喘组（分别咪0．204,0．284）明显高于健康对照组（分别为0．089,0．096,P＜0．01）,优势比（OR）分别为3．203（95％CI 1．699－6．037）和5．328（95％CI 2．883－9．849）,相反,HLA－DQA1＊0301基因和HLA－DQB1＊0301基因在哮喘组（0．148,0．20）,明显低于健康对照组（0．25,0．282,P＜0．01,P＜0．05）,HAL－DQA1＊0401基因与哮喘发病的独立危险因素分析显示P＜0．05,OR为5．0942（95％CI1．2252－21．1813）,HLA－DQA1＊0401基因和HLA－DQB1＊0201基因与特应质的相关系数分别为0．183,0．289,P＜0．01,而HLA1－DQA＊0301等位基因与特应质的相关系数为－0．168,P＜0．05,HLA－DQA1,HLA－DQB1基因与哮喘家系连锁分析LOD值＜1。结论：HLA－DQA1＊0104基因和HLA－DQB1＊0201基因与我国北方汉族哮喘者易感性相关,并且HLA－DQA1＊0104基因为哮喘发病的独立危险因素,而HLA－DQA1＊0301基因和HLA－DQB1＊0301基因则与哮喘的抗性相关。HLA－DQ基因对机体的特异性免疫应答有调节作用。

Relationship between HLA-DQA1, -DQB1 genes polymorphism and susceptilibity to bronchial asthma among Northern Hans

Objective To investigate the relationship between human leukocyte antigen (HLA) DQA1, DQB1 genes polymorphism and susceptibility to bronchial asthma among the Hans in the northen China. Method Sequence specific primer polymerase chain reaction was used to gene frequenncies of HLA DQA1 and HLA DQB1 genes among 125 unrelated asthmatics, 12 of which being probands of asthmatic pedigrees, and 96 healthy controls, all of Han nationality and living in Beijing or nearby areas for a long time. Radioimmunosorbent test was used to examine the serum IgE and TigE. The ventilatory functin was test among the asthmatics. Results The frequencies of HLA DQA1 0104 and HLA DQB1 0201 were 0.204 and 0.284, isgnificantly higher than those in the healthy controls (0.089 and 0.096 respectively, both P <0.01). Conversely, the frequencies of HLA DQA10301 and HLA DQB101301 in the asmatics were 0.148 and 0.20, significantly lower than those in the controls (0.25 and 0.282 respectively, P <0.01 and <0.05). The correlation coefficients between HLA DQA1*0104 and atopy, HLA DQB1*0201 and atopy, and HLA DQA1*0301 and atopy were 0.813 ( P <0.01), 0.289 ( P <0.01), and -0.168 ( P <0.05) respectively. Multi variate logistic regression asthma. Conclusions The alleles HLA DQA1*0104 and HLA DQB1*0201 are correlated with the susceptibility to asthma among Northers of Han nationality. HLA DQA1*0104 is an independent risk factor of onset of asthma. The alleles HLA DQA1*0301 and HLA DQB10301 are correlated with resistance against asthma. HLA DQ genes are involved in the regulation of human specific immune responses.