人类白细胞抗原-DR基因多态性与哮喘儿童IgE水平的关系

Association between Human Leukocyte Antigen DR gene polymorphisms and total IgE levels in children with asthma

目的探讨哮喘儿童人类白细胞抗原（HLA）-DR基因多态性与血清总IgE水平的关系。方法将无血缘关系的84例哮喘儿童和168名无哮喘和特应性疾病的健康个体纳入研究。采用Pharmacia UniCAP系统检测两组儿童的血清总IgE，同时完成10种吸入性过敏原皮肤实验。应用基因芯片法检测HIJA．DR的21个基因位点。结果（1）哮喘组HLA-DRB1＊070X基因和HLA-DRB1％11XX基因频率（分别为2．98％和13。69％）高于健康对照组（分别为0．30％和5．95％，矿值分别为6．915和9．478，P〈0．05或0．01），OR分别为10．57（95％CI1．215～91．986）和2．79（95％CI1．429—5．449）；HLA-DRB3（52）＋010X基因频率在哮喘组为7．14％，低于健康对照组（13．99％，X2=5．854，P〈0．05），OR为0．429（95％CI0．214～0．862）。（2）HLA-DRB1＊160XX和HLA—DRB1女3（17）两个等位基因与哮喘儿童的血清IgE水平高低相关（P〈0．05），HLA-DRB1＊160XX的OR值为0．145，95％CI为0．027—0．781；HLA-DRB1＊3（17）的OR值为1．667，95％CI为1．367—2．033。结论HLA．DRB1＊070X基因和HIA．DRB1＊11XX基因与儿童哮喘易感性相关，而HLA-DRB3（52）＊010X基因可能为保护性基因，HLA．DRB1＊160XX和HLA—DRB1＊3（17）等位基因与哮喘儿童的血清IgE水平相关，HLA-DRB1＊160XX可能是高水平血清IgE抗性基因，HLA—DRB1＊3（17）则是易感基因。

Objective To investigate the association between Human Leukocyte Antigen DR （HLA- DR） gene polymorphisms and total IgE levels in children with asthma. Methods This study involved 84 unrelated children with asthma and 168 healthy controls without asthma. All participants had their serum total IgE levels measured with UniCAP Pharmacia system, and skin-prick test with ten kinds of inhalant allergens were taken among them. HLA oligonucleotide array was used to determine twenty-one gene frequencies of HLA- DR. Results （ 1 ） The frequencies of HLA-DRB1 ＊ 070X allele and HLA-DRB1 ＊ llXX allele among the asthmatic were significantly higher than those in the healthy controls （HLA-DRB1 ＊ 070X allele： 2. 98% vs. 0. 30% ,Х^2 =6.915, P 〈0.05;HLA-DRB1 ＊ llXX allele：13.69% vs. 5.95% ,Х^2 =9.478, P 〈0.01）, Odds ratios （ OR ） for the two groups were 10. 57 （ 95 % CI. 1.215 - 91. 986） and 2. 79 （ 95 % CI： 1. 429 - 5. 449 ） respectively. HLA-DRB3（ 52 ） ＊ 010X allele were significantly decreased in asthmatics compared to healthy eontrols（ 13.99%, Х^2 = 5. 854, P 〈 0.05 ）, OR was 0. 429 （95 % CI：0. 214 - 0. 862 ）. （ 2 ） Significant correlation between HLA-DRB1 ＊ 160XX, HLA-DRB1 ＊ 3 （ 17 ） alleles and the level of total IgE were found in asthmatic children（ P 〈 0.05 ）. OR were 0. 145 （ 95% CI：0. 027 - 0. 781 ） for HLA-DRB1 ＊ 160XX allele and 1. 667 （ 95% CI： I. 367 - 2. 033 ） for HLA-DRBI ＊ 3 （ 17 ） allele. Conclusion HLA-DRBI ＊ 070X allele and HLA-DRBI ＊ llXX allele were implicated in susceptibility to asthma, HLA-DRB3 （52） ＊ 010X allele might conferring protection effects against asthma. There were association between HLA-DRB1 ＊ 160XX, HLA-DRB1 ＊ 3（17） alleles and the level of total IgE in asthmatic children. Protective effects of HLA-DRB1 ＊ 160XX allele against high level IgE response was noted, while HLA-DRB1 ＊ 3 （17）allele might be associated with high level of IgE in patients with asthma.