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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 analyze the genetic distribution of HLA gene in children with asthma in Guangxi through the detection of human leukocyte antigen (HLA) gene. Methods Eighty-four asthmatic children living in Guangxi, without blood relationship, were selected as the study group. 168 healthy individuals without asthma and atopic diseases were selected as the control group. PharmciaUniCAP system was used to detect serum total IgE levels in asthmatic children and 10 skin allergen tests and pulmonary function tests were performed at the same time. 27 genes of HLA-B and 21 loci of HLA-DR were detected by gene chip method. Results The frequencies of HLA-B56 allele and HLA-B58 allele in bronchial asthma group (5.36% and 14.28%, respectively) were significantly higher than those in healthy controls (0.89% and 8.04% respectively) (χ2 = 9.844, P <0.01; χ2 = 5.421, P <0.05); OR was 6.6 (95% confidence interval 1.737 ~ 25.076) and 2.09 (95% confidence interval 1.115 ~ 3.912) respectively. The HLA-B46 allele and HLA-B61 allele frequencies in asthma group (6.55% and 1.19%, respectively) were lower than those in the control group (12.80% and 4.76%, respectively) with statistically significant differences (χ2 = 5.197 and 4.308, P <0.05). OR was 0.438 (95% confidence interval 0.213-0.902) and 0.232 (95% confidence interval 0.055-1.100, respectively). The frequencies of HLA-DRB1 * 070X allele and HLA-DRB1 * 11XX allele (2.98% and 13.69%, respectively) in bronchial asthma group were significantly higher than those in control group (0.3% and 5.95%, respectively) χ2 = 6.915, P <0.05; χ2 = 9.478, P <0.01) OR were 10.57 (95% confidence interval 1.215-91.986) and 2.79 (95% confidence interval 1.429-5.449) respectively. The frequency of allele HLA-DRB3 (52) * 010X in asthma group was 7.14% lower than that in control group (13.99%), the difference was statistically significant (χ2 = 5.854, P <0.05); OR was 0.429 (95% confidence interval 0.214 ~ 0.862). Conclusion HLA-B56 and HLA-58 alleles, HLA-DRB1 * 070X and HLA-DRB1 * 11XX alleles are associated with susceptibility to asthma in children and are risk factors for asthma pathogenesis. HLA-B46 alleles and The HLA-DRB3 (52) * 010X allele may be protective against the body.