ABSTRACT
Objective Childhood asthma is closely related to MP infection.This study was to investigate the distribution of ORMDL3 and HLA-DQ gene SNP in children with MP-associated asthma and gene-gene interactions.Methods One hundred and ninety-four patients with MP infection were enrolled.Extraction of whole blood genomic DNA was carried out.The genotype was collected by Flnidigm Juno 96.96 Genotyping integrated fluid pathway system.The patients were divided into MP-asthma group and MP-non-asthma group.Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction.Results MP-asthma group included 63 cases (32.5％),MP-non asthma group included 131 cases (67.5％).ORMDL3 gene rs4794820 had three genotypes of AG,GG,AA.,MP-asthma group GG genotype and G allele frequency was higher than that in MP-non-asthma group.The frequency of AA genotype was the lowest among the two groups,but in the MP-non-asthma group were higher than that in the MP-asthma group.The rs7216389 had three genotypes of TT、TC、CC,the frequency of TT genotype and T allele in MP-asthma group was significantly higher than that in MP-non-asthma group.The frequency of CC genotype was the lowest among the two groups,but CC genotype in MP-non-asthma group was significantly higher than that in MP-asthma group.The rs794820 GG genotype and rs7216389 TT genotype were found to be risk factors.ORMDL3、HLA-DQA1 and HLA-DQA2 have gene-gene interaction.Conclusion MP infection is an important external cause of asthma in children.The genotype of rs7794820 GG genotype and rs7216389 TT genotype are an important internal cause of asthma after childhood MP infection.ORMDL3 rs4794820,rs7216389 and HLA-DQA1 rs9272346,HLADQA2 rs7773955 have gene-gene interaction,synergistically enhance the risk of asthma associated with asthma in children with MP.
ABSTRACT
Objective To discuss the polymorphisms of asthma susceptibility gene ORMDL3 in infantile wheezing,in order to provide a theoretical basis for early diagnosis of asthma.Methods One hundred and fifty wheezing infants were recruited and divided into 2 groups as asthma predictive index(API) positive group(n =80) and negative group (n =70).Taqman probe was applied to detect the genotypes of 2 single nucleotide polymorphisms (SNPs)in childhood asthma susceptibility gene ORMDL3,which were rs4794820 and rs7216389.The genotype distributions were analyzed and compared between 2 groups,and the correlations among genotype distribution and tidal breath pulmonary function,fractional exhaled nitric oxide (FeNO) concentration,percentage of eosinophils (EOS％),serum immune globulin E (total IgE) levels respectively were also analyzed,respectively.Results (1) The frequencies of rs4794820 AG and rs7216389 TC heterozygotes in the API positive group were the highest,which were significantly higher than those in the negative group(58.75％ vs.31.42％,56.25％ vs.32.86％ respectively,all P ＜0.01).The frequencies of GG and TT homozygotes in the API negative group were the highest,which were significantly higher than those in the positive group (58.57％ vs.30.00％,57.14％ vs.31.25％ respectively,all P ＜0.01).(2)The time to reach the peak expiratory flow in tidal breathing over the total expiratory time (TPTEF/TE) and the volume to reach the peak expiratory flow in tidal breathing over the total expiratory volume (VPEF/VE) of the infants in the API positive group were less than those in the API negative group(16.87 ±5.31 vs.20.12 ± 5.23,20.87 ± 5.92 vs.25.56 ± 6.77,respectively),and the FeNO concentration was higher than that in the API negative group [(22.44 ± 9.77) ppb vs.(13.23 ± 7.90)ppb],and the differences were significant (t =-3.776,-4.490,6.377,respectively;all P ＜ 0.01).(3) In the API positive group,the TPTEF/TE and VPEF/VE of the infants who expressed AG/TC genotype were lower than those who expressed GG/TT genotype (14.55 ± 4.83 vs.19.91 ± 4.17,18.85 ± 4.26 vs.25.20 ± 7.06,respectively,t =-4.727,-3.976,all P ＜ 0.01);while the FeNO concentrations,EOS％ and total IgE levels were higher than those who expressed GG/TT genotype [(25.02 ± 8.77) ppb vs.(18.39 ± 6.56) ppb,7.16 ± 2.62 vs.5.50 ± 1.34,(366 727 ±275 533) IU/L vs.(166 826 ± 62 865) IU/L,respectively] (t =3.484,3.409,4.589 respectively;all P ＜ 0.01).Conclusions Childhood asthma susceptibility gene ORMDL3 SNPs rs4794820 AG and rs7216389 TC heterozygotes are the risk factors for API positive infantile wheezing.The pulmonary function damage and airway inflammation of the infants who expressed AG/TC genotype are more serious than those who expressed GG/TT genotype,and more likely to develop persistent asthma.