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目的探讨广西壮、汉族人类白细胞抗原(HLA)-B、-DR位点的基因多态性与儿童哮喘发病的关联性。方法将3代居住广西南宁地区无血缘关系的84例哮喘儿童(汉族57例,壮族27例)和168例无哮喘和特应性疾病的健康人(汉族83例,壮族85例)纳入研究。所有哮喘儿童应用强生法玛西亚系统检测其血清总IgE水平、10种吸入性变应原皮肤点刺试验和肺功能检测。利用基因芯片法检测HLA-B的40个和HLA-DR的26个等位基因。分别计算汉族和壮族人群中哮喘和健康对照组基因频率,进行χ2检验,分别比较组间基因频率差异和危险性分析,计算基因与哮喘的关联强度比值比(OR值)。结果HLA-B位点共检出27个等位基因,HLA-DR检出21个等位基因。HLA-B46、HLA-DRB1*070X和HLA-DRB1*11XX等位基因仅在汉族的哮喘与健康人群分布有差异,哮喘与健康对照组比较有显著差异(Pa<0.05),OR值(95%CI)分别为0.388(0.153~0.983)、7.885(0.896~69.399)和2.782(1.188~6.516),且HLA-DRB1*070X等位基因在本组壮族人群中未见出现。壮族人群中,HLA-B56、-B61和-DRB1*1001等位基因在哮喘与健康对照组间有分布差异,哮喘与健康对照组比较有显著差异,组间HLA-B56经χ2检验有统计学意义(χ2=6.588P<0.01),HLA-DRB1*1001经Fisher精确概率法检验有统计学意义(P=0.043);HLA-B56和HLA-DRB1*1001的OR值(95%CI)分别为9.432(1.713~51.932)和10.50(1.044~105.590)。而HLA-B61等位基因在壮族哮喘患者中未见出现。结论HLA-B和HLA-DR的基因多态性在壮、汉族间分布有差异;HLA-B56和HLA-DRB1*1001等位基因可能为壮族人群的哮喘易感基因;而汉族人群中HLA-DRB1*070X和HLA-DRB1*11XX等位基因是易感基因,HLA-B46等位基因可能为保护基因。
Objective To investigate the association between genetic polymorphisms of human leukocyte antigen (HLA) -B and -DR loci in Zhuang and Han nationalities in Guangxi and the incidence of childhood asthma. Methods A total of 84 asthmatic children (57 Han and 27 Zhuang nationality) and 168 healthy people without asthma and atopic diseases (83 Han and 85 Zhuang nationality) were enrolled in the study. All asthmatic children were tested for total serum IgE levels, 10 inhaled allergens skin prick tests, and lung function tests using the Johnson & Johnson Familys system. 40 alleles of HLA-B and 26 alleles of HLA-DR were detected by gene chip method. The frequencies of genes in asthmatic and healthy controls were calculated respectively by Han and Zhuang populations, and theχ2 test was performed. The differences in gene frequency and risk were compared among groups, and the odds ratio (OR) was calculated. Results A total of 27 alleles were detected in HLA-B locus and 21 alleles were detected in HLA-DR. The distribution of HLA-B46, HLA-DRB1 * 070X and HLA-DRB1 * 11XX alleles was only different between Han nationality and healthy population. There was significant difference between asthma group and healthy control group (P0.05) CI) were 0.388 (0.153-0.983), 7.885 (0.896-69.399) and 2.782 (1.188-6.516), respectively. No HLA-DRB1 * 070X alleles were found in this group of Zhuang people. Zhuang population, HLA-B56, -B61 and -DRB1 * 1001 alleles in the asthma and healthy control group distribution differences, asthma and healthy control group were significantly different, between groups by χ2 test HLA-B56 statistics (P = 0.043). The OR values (95% CI) of HLA-B56 and HLA-DRB1 * 1001 were significantly higher than that of HLA-DRB1 * 1001 9.432 (1.713 ~ 51.932) and 10.50 (1.044 ~ 105.590). The HLA-B61 allele in Zhuang asthma patients have not seen. Conclusion HLA-B and HLA-DR gene polymorphisms are distributed in Zhuang and Han ethnic groups. HLA-B56 and HLA-DRB1 * 1001 alleles may be susceptible genes for asthma in Zhuang ethnicity. However, HLA- DRB1 * 070X and HLA-DRB1 * 11XX alleles are susceptible genes, HLA-B46 alleles may be protective genes.