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  

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

作　　者：高金明[1] 林耀广[1] 邱长春[2] 刘怡雯[2] 马毅[1] 高君[1] 刘英[2] 

机构地区：[1]中国协和医科大学中国医学科学院北京协和医院呼吸科,100730 [2]医学分子生物学国家重点实验室

出　　处：《中华医学杂志》2002年第6期379-383,共5页National Medical Journal of China

基　　金：国家"九.五"攻关基金资助项目 (96 90 6 0 2 0 4) ;高等学校博士学科专项科研基金资助项目 (980 3 )

摘　　要：目的　探讨人类白细胞抗原 (HLA) 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 12 5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 0 10 4基因和HLA DQB1 0 2 0 1基因频率在哮喘组 (分别为 0 2 0 4 ,0 2 84 )明显高于健康对照组 (分别为 0 0 89,0 0 96 ;P <0 0 1) ,优势比 (OR)分别为 3 2 0 3(95 %CI 1 6 99～ 6 0 37)和 5 32 8(95 %CI 2 883 9 84 9)。相反 ,HLA DQA1 0 30 1基因和HLA DQB1 0 30 1基因频率在哮喘组 (0 14 8,0 2 0 )明显低于健康对照组 (0 2 5 ,0 2 82 ;P <0 0 1,P <0 0 5 )。HLA DQA1 0 10 4基因与哮喘发病的独立危险因素分析显示P <0 0 5 ,OR为 5 0 94 2 (95 %CI1 2 2 5 2～ 2 1 1813)。HLA DQA1 0 10 4基因和HLA DQB1 0 2 0 1基因与特应质的相关系数分别为 0 183,0 2 89,P <0 0 1;而HLA1 DQA 0 30Objective 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.

关 键 词：支气管哮喘 白细胞抗原 DQA1 DQB1 基因多态性 遗传易感性 聚合酶链反应 汉族 中国 

分 类 号：R562.25[医药卫生—呼吸系统]