摘要
Objective Human leukocyte antigen (HLA) class Ⅱ genes, especially HLA DQ genes, which are highly polymorphic, have been thought to be candidate loci for the etiology of asthma, and shown to be involved in antigenic presentation This study was conducted to investigate whether susceptibility or resistance to asthma is associated with HLA DQA1 and DQB1 genes polymorphism Methods Venous blood samples were collected from northern Chinese population with Han ethnic (1) One hundred and twenty five unrelated asthmatic individuals and 52 subjects from 12 asthmatic pedigrees (2) Ninety six healthy controls without asthma and atopy with the same ethnic Genomic DNA was extracted using standard phenol chloroform method The second exon of HLA DQA1 and DQB1 genes were amplified by sequence specific primer polymerase chain reaction (SSP PCR) method All asthmatics had their serum IgE (total and specific) antibody or skin prick test measured, bronchial reactivity to methacholine (Mch) and bronchial reversibility by β 2 agonist evaluated Results HLA DQA1*0104 allele and HLA DQB1*0201 allele were significantly higher in asthmatics than those in healthy controls (0 408 vs 0 177, P <0 01; 0 568 vs 0 198, P <0 01) Odds ratios (ORs) were 3 203 (95% CI 1 699-6 037), 5 328 (95% CI 2 883-9 849) respectively Conversely, HLA DQA1*0301 allele and HLA DQB1*0301 were significantly decreased in asthmatics compared to healthy controls (0 296 vs 0 50, P <0 01; 0 4 vs 0 563, P <0 05); Logistic regression analysis showed that HLA DQA1*0104 allele was associated independently with asthma etiology, OR [represented by Exp(B)] was 5 0942 with 95% CI 2 2520 21 1813; Spearman's analysis showed that HLA DQA1*0104 allele and HLA DQB1*0201 allele were positively associated with atopy, the correlation coefficient were 0 183 and 0 289 respectively, P <0 01 By contrast, HLA DQA1*0301 allele was negatively related to atopy, the correlation coefficient was -0 168, P <0 05; linkage analysis did not support the view that HLA DQA1/DQB1 genes were linked to asthma with LOD value being 0 72 Conclusions HLA DQA1*0104 allele and HLA DQB1*0201 allele were implicated in susceptibility to asthma and atopy, HLA DQA1*0301 allele and HLA DQB1*0301 might be protective factor against asthma Asthma and atopy are multifactorial disorders, HLA DQA1 and DQB1 genes are involved in the regulation of immune specific response to common allergen
Objective Human leukocyte antigen (HLA) class Ⅱ genes, especially HLA DQ genes, which are highly polymorphic, have been thought to be candidate loci for the etiology of asthma, and shown to be involved in antigenic presentation This study was conducted to investigate whether susceptibility or resistance to asthma is associated with HLA DQA1 and DQB1 genes polymorphism Methods Venous blood samples were collected from northern Chinese population with Han ethnic (1) One hundred and twenty five unrelated asthmatic individuals and 52 subjects from 12 asthmatic pedigrees (2) Ninety six healthy controls without asthma and atopy with the same ethnic Genomic DNA was extracted using standard phenol chloroform method The second exon of HLA DQA1 and DQB1 genes were amplified by sequence specific primer polymerase chain reaction (SSP PCR) method All asthmatics had their serum IgE (total and specific) antibody or skin prick test measured, bronchial reactivity to methacholine (Mch) and bronchial reversibility by β 2 agonist evaluated Results HLA DQA1*0104 allele and HLA DQB1*0201 allele were significantly higher in asthmatics than those in healthy controls (0 408 vs 0 177, P <0 01; 0 568 vs 0 198, P <0 01) Odds ratios (ORs) were 3 203 (95% CI 1 699-6 037), 5 328 (95% CI 2 883-9 849) respectively Conversely, HLA DQA1*0301 allele and HLA DQB1*0301 were significantly decreased in asthmatics compared to healthy controls (0 296 vs 0 50, P <0 01; 0 4 vs 0 563, P <0 05); Logistic regression analysis showed that HLA DQA1*0104 allele was associated independently with asthma etiology, OR [represented by Exp(B)] was 5 0942 with 95% CI 2 2520 21 1813; Spearman's analysis showed that HLA DQA1*0104 allele and HLA DQB1*0201 allele were positively associated with atopy, the correlation coefficient were 0 183 and 0 289 respectively, P <0 01 By contrast, HLA DQA1*0301 allele was negatively related to atopy, the correlation coefficient was -0 168, P <0 05; linkage analysis did not support the view that HLA DQA1/DQB1 genes were linked to asthma with LOD value being 0 72 Conclusions HLA DQA1*0104 allele and HLA DQB1*0201 allele were implicated in susceptibility to asthma and atopy, HLA DQA1*0301 allele and HLA DQB1*0301 might be protective factor against asthma Asthma and atopy are multifactorial disorders, HLA DQA1 and DQB1 genes are involved in the regulation of immune specific response to common allergen
基金
NationalSciencesandTechnologyCommissionofChina (No 90 6 96 0 2 0 4)
