Research On Association Of Single Nucleotide Polymorphisms In ORMDL3Gene With Bronchiolitis In A Chinese Population

Background and objective:It is widely reported that infants hospitalized with bronchiolitis are atsignificantly increased risk for both recurrent wheezing and childhoodasthma. Recent studies confirmed that there are common genetic risks forboth bronchiolitis and asthma. Single nucleotide polymorphism (SNP)based on genomewide association study revealed that markers onchromosome17q21were linked to childhood asthma, with the strongestsignal being detected for the SNP rs7216389in the ORMDL3gene.However, the genetic association between ORMDL3and bronchiolitissusceptibility remains unknown. Besides，respiratory syncytial virus (RSV)and human rhinoviruses (HRV) are the most important causes ofbronchiolitis in infants，which is independent risk factor for subsequentwheeze and asthma. The purpose of this study was to assess the associationbetween the ORMDL3polymorphism and bronchiolitis susceptibility andviral infection. Methods:247children with physician-diagnosed bronchiolitis were enrolledfrom Children’s Hospital of Chongqing Medical University from June2009to December2012.190healthy outpatient children were enrolled in thecontrol group. Three SNPs on17q21region were genotyped bymatrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF). Respiratory viruses were detected with multiplex reversetranscriptase polymerase chain reaction. Further，the bronchiolitis groupwere divided into subgroups according to the clinical manifestationsand types of virus detected. To test the association of each locus withbronchiolitis susceptibility and severity and viral infections，we comparedcases and controls in terms of allele frequency and genotype distributionfor each polymorphism.Results:Only the genotype and allele frequencies of rs7216389weresignificantly different between bronchiolitis and controls. The TThomozygote and the T allele of rs7216389were significantly higher inbronchiolitis patients group (P=0.0325；P=0.0089，respectively). Neither ofthe SNPs was associated with the severity of bronchiolitis. Cases werefurther stratified by viruses detection，there were no significant differencesin genotype frequencies of the three SNPs between virus-detected groupand no-virus detected group [rs12603332(χ2=1.7483；P=0.4172)，rs7216389(χ2=1.8822；P=0.3902)， rs11650680(χ2=1.3025；P=0.5214)]. In addition，no significant differences in the genotype of the three SNPswere observed between single-RSV detected group and no-virus detectedgroup [rs12603332(χ2=1.3435；P=0.5108)，rs7216389(χ2=1.0062；P=0.6047)，rs11650680(χ2=1.7766；P=0.4113)]. Comparison of thesingle-HRV detected group and the no-virus detected group showed thatthere were no significant associations with the ORMDL3variants[rs12603332(χ2=0.6648；P=0.7172)，rs7216389(χ2=0.5514；P=0.759)，rs11650680(χ2=5.3372；P=0.0693)].Conclusions:Bronchiolitis are associated with ORMDL3variants in Chinesechildren，and there were no correlation between ORMDL3variations anddesease severity or respiratory viruses. The TT homozygote and T allele ofrs7216389in ORMDL3will increse the risk of bronchiolitis for Chinesechildren.