人类白细胞抗原-DR及-G基因多态性与广西儿童哮喘发病的研究

Study on the association between Human Leukocyte antigen gene-DR and -G polymorphisms and children asthma in Guangxi

目的探讨人类白细胞抗原(HLA)-DR及-G基因多态性与儿童哮喘的关系。方法以无血缘关系的84例哮喘儿童为哮喘组,168名无哮喘和特应性疾病的健康个体为对照组。采用Pharmacia UniCAP系统检测哮喘儿童的血清总IgE水平。应用基因芯片法检测HLA-DR的21个基因位点和基于基质辅助激光解吸电离-飞行时间质谱技术(MALDI-TOF)检测HLA-G的9个单核苷酸位点。结果 (1)儿童哮喘组HLA-DRB1*070X基因和HLA-DRB1*11XX基因频率分别为2.98%和13.69%,对照组分别为0.3%和5.95%(χ2=6.915,P<0.05;χ2=9.478,P<0.01)。优势比(OR?)分别为10.57(95%CI:1.215～91.986)和2.79(95%CI:1.429～5.449)。HLA-DRB3(52)*010X基因频率在哮喘组为7.14%,低于对照组的13.99%(χ2=5.854,P<0.05),OR?为0.429(95%CI:0.214～0.862)。(2)HLA-DRB1*15XX-HLA-G的rs1704和rs1063320位点的14bp缺失-G单体型(HLA-DRB1*15XX-14bp缺失-G)携带者哮喘风险比未携带者降低(Wald值为13.419,P<0.001),OR?值为0.198,95%CI为0.084～0.471;哮喘组中携带该单体型者血清IgE水平(365.0±943.1)KU/L,也较未携带者(977.8±14334.9)KU/L为低,差异有统计学意义(P<0.05)。结论 HLA-DRB1*070X基因和HLA-DRB1*11XX基因与儿童哮喘易感性相关,HLA-DRB3(52)*010X基因可能为保护性基因,HLA-DRB1*15XX和HLA-G的rs1704和rs1063320位点的14bp缺失-G单体型是哮喘的保护性单体型。

Objective To investigate the association between Human Leukocyte antigen DR（HLA-DR） gene polymorphisms and asthma in children. Methods Eighty-four unrelated asthmatic children and one hundred and six- ty-eight healthy controls without asthma and atopy were involved in the study. All asthmatics had their serum total IgE levels measured with UniCAP Pharmacia system were taken among the asthmatic children. HLA oligonucleotide array was used to detect twenty-one gene frequencies of HLA-DR, and massARRAY system （Sequenom） by means of ma- trix assisted laser desorption ionisation-time of flight mass spectrometry method（MALDI-TOF） for HLA-G gene single nucleotide poly -morphism （SNP） genotyping. Results （ 1 ） The frequencies of HLA-DRB1 ＊ 070X allele and HLA- DRB1 ＊ llXX allele in the asthmatic childeru were 2. 98% and 13.69%, significantly higher than those in healthy controls （0.3% and 5.95%, ）（2 =6.915,P〈0.05; ,y2 =9.478,P 〈0.01）, Odds ratios （Ors） 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 signifi- cantly decreased in asthmatics compared to healthy controls （ 13.99%, ）（2 = 5. 854, P 〈 0. 05 ）, Ors were 0. 429 （95% CI：O. 214 ~0. 869）. （2）The individuals with HLA-DRB1 ＊ 15XX-rsl704/rs 1063320 locus and 14-bp deletion/G haplotype was lower asthmatics risk than those without the same haplotype, and Ors was 0. 198 （95% CI：0. 084 0. 471 ）, also the level of serum value of IgE in asthmatic children were significantly lower than those without the haplotype of rs1704/rs1063320 14-bp deletiort/G （ P 〈 0.05 ）. Conclusion HLA-DRB1 ＊ 070X allele and HLA- DRB1 ＊ 11XX allele were implicated in susceptibility to asthma, HLA-DRB3 （52） ＊ 010X allele might confer protection against asthma. And the haplotype of HLA-DRB1 ＊ 15XX- rs1704/rs1063320 14-bp deletiort/G are protective from children asthma.