ORMDL3基因多态性与儿童哮喘发病的关系

Association of polymorphisms of ORMDL3 gene with children asthma

目的探讨ORMDL3基因的单核苷酸多态性（SNPs）与汉族儿童哮喘发病的相关性。方法选取儿童哮喘患者168例和同期健康查体者188例为研究对象,利用MassARRAY-IPLEX技术和基质辅助激光解吸电离飞行时间质谱平台（MALDI-TOF-MS）对ORMDL3基因的7个SNPs位点进行基因分型。结果与对照组相比,哮喘组嗜酸性粒细胞计数（Z=26.581,P=0.000）和IgE明显升高（Z=73.208,P=0.000）,CRP水平差异无统计学意义（Z=2.938,P=0.066）,吸入性过敏原（χ2=44.638,P=0.000）和食物过敏原（χ2=14.347,P=0.000）检出率明显增高。总的基因型分型成功率为99.34%。与对照相比,哮喘组rs4795400的等位基因分布（χ2=4.166,P=0.041）有差异,但基因型分布（χ2=3.732,P=0.155）无明显差异。与对照相比,哮喘组rs2305480和rs3859192的等位基因分布（χ2=5.294,P=0.021;χ2=6.804,P=0.009）有差异,基因型分布（χ2=5.538,P=0.019;χ2=7.618,P=0.022）也均具有显著性差异,但进行Bonferroni校正后两组间基因型分布均无显著性差异（Pc=0.114;Pc=0.132）。与对照相比,哮喘组rs7216389、rs8069176和rs12603332的等位基因分布（χ2=13.800,P=0.000;χ2=13.066,P=0.000;χ2=10.872,P=0.001）均具有显著差异,基因型分布（χ2=12.162,P=0.002;χ2=11.574,P=0.003;χ2=10.500,P=0.005）同样均具有显著性差异,进行Bonferroni校正后两组间仍均具有显著性差异（Pc=0.012;Pc=0.018;Pc=0.030）。与CC基因型相比,rs7216389的TT基因型显著增加哮喘发生的危险性（P=0.003）,OR值（95%可信区间）为3.846（1.488~9.939）。与AA基因型相比,rs8069176的GG基因型显著增加哮喘发生的危险性（P=0.008）,OR值（95%可信区间）为3.453（1.322~9.017）。与TT＋TC基因型相比,rs12603332的CC基因型显著增加哮喘发生的危险性（P=0.001）,OR值（95%可信区间）为2.057（1.316~3.214）。结论 ORMDL3基因的rs7216389、rs8069176和rs12603332位点与汉族儿童哮喘的发病有关。

Objective To investigate the association between single nucleotide polymorphisms（SNPs）of ORMDL3 and children asthma of Han Nationality in the Southern China.Methods A case-control study was performed.MassARRAY-IPLEX technique and MALDI-TOF-MS was used to determine 7 locus of ORMDL3 gene.Results There were no significant differences in gender（χ2=0.012,P=0.914） and age（t=1.710,P=0.088） between asthma group and control group,respectively.Compared with control group,eosinophil count（Z=26.581,P=0.000） and IgE（Z=73.208,P=0.000） in asthma group was significantly increased,no significant difference in CRP level（Z=2.938,P=0.066）,and while significant difference in Inhalant allergens（χ2=44.638,P=0.000） and food allergens（χ2=14.347,P=0.000）.99.34% percent of samples were genotyped.Compared with control group,there were significant differences in allele frequency（χ2=4.166,P=0.041）and no significant differences in genotype frequency（χ2=3.732,P=0.155） of rs4795400 in asthma group.Compared with control group,allele frequency（χ2=5.294,P=0.021;χ2=6.804,P=0.009） and genotype frequency（χ2=5.538,P=0.019;χ2=7.618,P=0.022）of rs2305480 and rs3859192 in asthma group were significantly different,respectively,but after Bonferroni correction no significant difference（Pc=0.114;Pc=0.132） were showed in genotype frequency between the two groups.Compared with control group,allele frequency（χ2=13.800,P=0.000;χ2=13.066,P=0.000;χ2=10.872,P=0.001）and genotype frequency（χ2=12.162,P=0.002;χ2=11.574,P=0.003;χ2=10.500,P=0.005）of rs7216389 and rs8069176 and rs12603332 in asthma group were significantly different,respectively,and after Bonferroni correction there were still significant difference（Pc=0.012;Pc=0.018;Pc=0.030） in genotype frequency between the two groups.Compared with genotype CC,genotype TT of rs7216389 could significantly increase the risk of asthma,which odds ratio（95% confidence interval）were 3.846（1.488-9.939）.Compared with genotype AA,genotype GG ofrs8069176 could significantly increase the risk of asthma,which odds ratio（95%confidence interval）were 3.453（1.322-9.017）.Compared with genotype TT＋TC,genotype CC of rs12603332 could significantly increase the risk of asthma,which odds ratio（95%confidence interval）were 2.057（1.316-3.214）.Conclusion These researches suggest that Locus rs7216389 and rs8069176 and rs12603332 of ORMDL3 gene maybe take part in the pathogenesis of children asthma of Han Nationality.