Association between human leukocyte antigen gene polymorphisms and total immunoglobulin E levels in children with asthma

Abstract

Objective To investigate the association between human leukocyte antigen DR (HLA-DR) gene and HLA-G gene polymorphisms and total IgE levels in children with asthma. Methods Eighty-four unrelated asthmatic individuals and 168 healthy controls without asthma or atopy were involved in the study.All asthmatic children had their serum total IgE levels measured with UniCAP Pharmacia system, and skin-prick test with 10 kinds of inhalant allergens was taken among the asthmatics children.HLA oligonucleotide array was used to detect 21 gene frequencies of HLA-DR and mass ARRAY system (Sequenom) by means of matrix-assisted laser desorption ionisation, while time of flight mass spectrometry method was used for HLA-G gene single nucleotide polymorphism (SNP) genotyping. Results 1.The frequencies of HLA-DRB1*070X allele and HLA-DRB1*11XX allele among the asthmatics were 2.98% and 13.69%, which were significantly higher than those in healthy controls (0.30% and 5.95%, χ2 =6.915, P<0.05; χ2=9.478, P<0.01), and odds ratios (OR) were 10.570(95% CI: 1.215-91.986) and 2.790(95% CI: 1.429-5.449), respectively.HLA-DRB3(52)*010X allele was significantly decreased in asthmatic children compared to healthy controls(7.14% vs 13.99%, χ2=5.854, P<0.05), and OR were 0.429(95% CI: 0.214-0.869). HLA-DRB1*15XX allele were also significantly decreased in asthmatic children compared to healthy controls (16.67% vs 31.70%, χ2=13.491, P<0.01), and OR were 0.431(95% CI: 0.263-0.706).2.HLA-DRB1*160XX, HLA-DRB1*3(17) alleles and the level of total IgE in asthmatic children were significantly correlated (P<0.05). OR were 0.145(95% CI: 0.027-0.781)in HLA-DRB1*160XX allele and 1.667(95% CI: 1.367-2.033)in HLA-DRB1*3(17) allele.3.The individuals with HLA-DRB1*15XX-rs1704/rs1063320 locus and 14-bp deletion/G haplotype had lower asthmatic risk than that without the same haplotype, and OR was 0.198(95% CI: 0.084-0.471), also the level of serum IgE in asthmatic children [(365.00±943.10) kU/L] was significantly lower than that without the haplotype of rs1704/rs1063320 14 bp deletion/G [(977.80±14 334.90) kU/L](F=4.827, P<0.05). Conclusions HLA-DRB1*070X allele and HLA-DRB1*11XX allele were implicated in susceptibility to asthma, and HLA-DRB3(52)*010X allele and HLA-DRB1*15XX allele might confer protection against asthma.There was relevance between HLA-DRB1*160XX, HLA-DRB1*3(17) alleles and the level of total IgE in asthmatic children, and protection association between HLA-DRB1*160XX allele and high level IgE response was noted.While HLA-DRB1*3(17) allele might be implicated to high level IgE in patient with asthma.And, the haplotype of HLA-DRB1*15XX- rs1704/rs1063320 14 bp deletion/G is protective haplotype of asthma. Key words: Asthma; Human leukocyte antigen; Immunoglobulin E; Gene polymorphism; Child