ORMDL3和HLA-DQ基因多态性及交互作用在儿童肺炎支原体感染相关哮喘中的研究

Association of ORMDL3 and HLA-DQ single nucleotide polymorphisms in children with asthma associated Mycoplasma pneumoniae infection

目的 探究ORMDL3与HLA-DQ基因SNP在儿童MP感染相关哮喘中的分布情况及基因-基因交互作用.方法 选取MP感染住院患儿194例,提取全血基因组DNA,采用Fluidigm Juno96.96 Genotyping集成流体通路系统进行基因分型,随访观察1年,分为MP-哮喘组和MP-非哮喘组.广义多因子降维法分析基因-基因交互作用.结果 194例患儿中,MP-哮喘组63例(32.5％);MP-非哮喘组131例(67.5％).ORMDL3 rs4794820位点有AG、GG、AA3种基因型,MP-哮喘组的GG基因型和G等位基因频率明显高于MP-非哮喘组,两组间均以AA基因型频率最低;rs7216389位点有TT、TC、CC 3种基因型,MP-哮喘组的TT基因型和T等位基因频率明显高于MP-非哮喘组,两组间均以CC基因型频率最低.rs4794820位点GG基因型、rs7216389位点TT基因型为危险因素.ORMDL3rs4794820、rs7216389与HLA-DQA1 rs9272346、HLA-DQA2 rs7773955四个位点之间存在基因-基因交互作用.结论 MP感染是儿童哮喘的重要外因.ORMDL3基因rs4794820位点GG基因型,rs7216389位点TT基因型是儿童MP感染相关哮喘的重要内因.ORMDL3 rs4794820、rs7216389与HLA-DQA1rs9272346、HLA-DQA2 rs7773955四个SNP位点之间存在交互作用,协同增强了儿童MP感染相关哮喘的发病风险.

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.