广西支气管哮喘儿童HLA等位基因的研究

The study of HLA alleles in Guangxi children with bronchial asthma

目的通过人类白细胞抗原（HLA）基因检测,分析广西哮喘儿童HLA基因遗传分布情况。方法选择居住广西、无血缘关系的84例哮喘儿童为研究组,168例无哮喘和特应性疾病的健康个体为对照组。采用PharmciaUniCAP系统检测哮喘儿童的血清总IgE水平,同时完成10种吸入性过敏原皮肤实验和肺功能检查。应用基因芯片法检测HLA-B的27个和HLA-DR的21个基因位点。结果支气管哮喘组HLA-B56等位基因和HLA-B58等位基因频率（分别为5.36%和14.28%）明显高于健康对照组（分别为0.89%和8.04%）,差异有统计学意义（χ2=9.844,P〈0.01;χ2=5.421,P〈0.05）;OR分别为6.6（95%可信区间1.737-25.076）和2.09（95%可信区间1.115-3.912）。HLA-B46等位基因和HLA-B61等位基因频率哮喘组（分别为6.55%和1.19%）低于对照组（分别为12.80%和4.76%）,差异有统计学意义（χ2值为5.197和4.308,P〈0.05）;OR分别为0.438（95%可信区间0.213-0.902）和0.232（95%可信区间0.055-1.100）。支气管哮喘组HLA-DRB1＊070X等位基因和HLA-DRB1＊11XX等位基因频率（分别为2.98%和13.69%）高于对照组（分别为0.3%和5.95%）,差异有统计学意义（χ2=6.915,P〈0.05;χ2=9.478,P〈0.01）OR分别为10.57（95%可信区间1.215-91.986）和2.79（95%可信区间1.429-5.449）。HLA-DRB3（52）＊010X等位基因频率哮喘组为7.14%低于对照的的13.99%,差异有统计学意义（χ2=5.854,P〈0.05）;OR为0.429（95%可信区间0.214-0.862）。结论HLA-B56和HLA-58等位基因,HLA-DRB1＊070X和HLA-DRB1＊11XX等位基因与广西哮喘儿童易感性相关,为哮喘发病机制的危险因素;而HLA-B46等位基因和HLA-DRB3（52）＊010X等位基因对机体则可能有保护性。

Objective To investigate the genetic distinction of human leukocyte antigen （HLA） genes in Guangxi children with bronchial asthma. Methods Eighty four unrelated asthmatic individuals and one hundred and sixty healthy controls without astiuna and atopy living in Guangxi were involved in the study. Their serum total IgE levels were detected by IJniCAP Pharmacia system,and skin-prick testing for ten inhalant allergens were taken,pulmonary function were measured. HLA oligonucleotide array was used to detect twenty-seven gene frequencies of HLA-B and twenty-one HLA-DR. l/_esults The frequencies of HLA-B56 allele and HLA-B58 allele among the asthmatic were 5.36% and 14.28% ,which were significantly higher than those in healthy controls （0.89% and 8.04% ,χ^2 =9.844,P 〈0.01 and 5.421,P 〈0.05） ,Odds ratios （OR） were 6.6 （95% CI：1.737 - 25.076） and 2. 09 （95% CI：1.115 - 3. 912） respectively. HLA-B46 allele and HLA-B61 allele （6. 55% and 1.19% ） were sigifieantly decreased in asthmatics compared to healthy controls （12.80% and 4.76% ,χ^2 =5. 197 and 4.308,P 〈0.05） ,OR were 0.438 （95% （3：0.213 -0.902） and 0.323 （95% CI：0.055 -1.100）. HLA-DRB1.070X allele and HLA-DRB1 ＊ 11XX allele in the asthmatics were 2.98% and 13.69% ,which were higher than those in healthy controls （0.3% and 5.95% ,X2 =6.915,P 〈0.05 and 9.478,P 〈0.01） ,OR were 10.57 （95% CI：1.215 -91.986） and 2.79 （95% CI：1.429-5.449） respectively.The frequency of HLA-DRB3 （52） ＊010X allele was 7. 14% ,which was decreased in asthmaties compared to healthy controls （13.99%,χ^2 =5.854,P 〈0.05）,OR was 0.429 （95% CI：0.214-0.862）. Conclusion HLA-B56 allele and HLA-B58 allele, HLA-DRB1 ＊070X allele and HLA-DRB1 ＊ 11XX allele are implicated in susceptibility to asthma in Guangxl,they are risk factors of asthma pathogenesis. HLA-B46 allele and HLA-DRB3 （52） ＊010X allele might be protective factor against asthma.