Polymorphisms Of Asthma Susceptibility Gene HLA-DQ And ORMDL3 In Infantile Wheezing

Objective:To discuss the polymorphisms of asthma susceptibility gene HLA-DQA1,HLA-DQA2 and ORMDL3 in infantile wheezing,in order to provide a theoretical basis for early diagnosis of asthma.Method:One hundred and fifty wheezing infants were recruited and divided into two groups,API positive(n=80)or negative(n=70)groups.Juno system using the 96.96 IFCwere applied to detect the genotypes of four SNPs in childhood asthma susceptibility gene HLA-DQA1,HLA-DQA2 and ORMDL3,they were rs9272346,rs7773955,rs4794820 and rs7216389.The genotype distributions were analyzed and compared between the two groups,and the correlations between genotype distribution and tidal breath pulmonary function,fractional exhaled nitric oxide(FENO)concentration,percentage of eosinophils(EOS%),serum immune globulin E(total Ig E)level respectively were also analyzed.The interaction among the asthma susceptibility genes was discussed by GMDR.Result: 1.The frequencies of rs9272346 AG heterozygotes in the API positive group were the highest,and the AA homozygotes were the lowest.The frequencies of rs9272346 AG heterozygotes in the API negative group were the highest,and the GG homozygotes were the lowest.There were no significant differences found in the genotype distribution of rs9272346 between the two groups(P > 0.05 for all).2.The frequencies of rs7773955 CC homozygotes were the highestand the TT homozygotes were the lowest in two groups.The frequencies of rs7773955 CC homozygotes in the API positive group were significantly higher than those in the negative group,and the frequencies of TT homozygotes in the API negative group were significantly higher than those in the positive group(P<0.05 for all).3.The frequencies of rs4794820 AG heterozygotes in the API positive group were the highest,and the AA homozygotes were the lowest.The frequencies of rs4794820 GG homozygotes in the API negative group were the highest, and the AA homozygotes were the lowest.The frequencies of rs4794820 AG heterozygotes in the API positive group were significantly higher than those in the negative group,and the frequencies of GG homozygotes in the API negative group were significantly higher than those in the positive group(P<0.05 for all).4.The frequencies of rs7216389 TC heterozygotes in the API positive group were the highest,and the CC homozygotes were the lowest.The frequencies of rs7216389 TT homozygotes in the API negative group were the highest,and the CC homozygotes were the lowest.The frequencies of rs7216389 TC heterozygotes in the API positive group were significantly higher than those in the negative group,and the frequencies of TT homozygotes in the API negative group were significantly higher than those in the positive group(P<0.05 for all).5.The GMDR analysis showed that the best statistically significant interaction model including rs9272346,rs7773955,rs4794820 and rs7216389.The accuracy of the model was 0.6946,the result of cross validation was 10/10.The gene-gene interaction among rs9272346,rs7773955,rs4794820 and rs7216389 were independent risk factors of API positive infantile wheezing(OR=1.026,95%CI:1.006-1.046,P=0.011).6.In the API positive group,the TPTEF/TE and VPEF/VE of the infants who express AG/TC genotype of rs4794820 and rs7216389 were lower than those who express GG/TT genotype,while the FENO concentrations,EOS% and total Ig E levels were higher than those who express GG/TT genotype(P<0.01 for all).7.The infants’ TPTEF/TE and VPEF/VE in the API positive group were lower than those in the API negative group,and the Fe NO concentrations were higher than those in the API negative group(P<0.01 for all).8.There were no significant correlations found between FENO and TPTEF/TE,VPEF/VE(P > 0.05 for all).Conclusions: 1.Childhood asthma susceptibility gene HLA-DQA2 SNPsrs7773955 CC homozygotes,ORMDL3 SNPs rs4794820 AG and rs7216389 TC heterozygotes are the risk factors of API positive infantile wheezing.2.The pulmonary function damage and airway inflammation of the infants who express AG/TC genotype are more serious than those who express GG/TT genotype,and more likely to develop into severe wheezing.3.rs9272346,rs7773955,rs4794820 and rs72163895 can synergistically enhance the risk of wheezing infants to develop into persistent asthma.