儿童哮喘NR3C1基因单核苷酸多态性及对糖皮质激素疗效的影响分析

Single nucleotide polymorphisms of NR3C1 gene in childhood asthma and its influence on the efficacy of glucocorticoids

目的探讨糖皮质激素受体基因(NR3C1)单核苷酸多态性与儿童哮喘的关系及吸入性糖皮质激素(inhaled corticosteroid,ICS)疗效的分析。方法选取2018年10月至2020年10月于北部战区总医院住院治疗的儿童支气管哮喘患儿101例为哮喘组,100例健康体检儿童为对照组,提取所有入选儿童外周血DNA,采用SNaPshot SNP基因检测技术对糖皮质激素受体基因位点进行多态性分析,比较两组儿童rs41423247、rs7701443位点基因型频率及等位基因频率,对哮喘组患儿予ICS治疗12周时,比较不同基因型组哮喘治疗效果差异。结果rs41423247位点基因型GG/GC/CC频率分别为:哮喘组75.2%、21.8%、3.0%,对照组72.0%、24.0%、4.0%,两组比较差异无统计学意义(χ^(2)=0.333,P>0.05);rs7701443位点基因型GG/GA/AA频率分别为:哮喘组45.5%、39.6%、14.9%,对照组56.0%、31.0%、13.0%,两组比较差异无统计学意义(χ^(2)=2.259,P>0.05)。经ICS治疗后,rs41423247位点CC型哮喘患儿C-ACT/ACT评分较治疗前无显著升高(P>0.05),而GG型、GC型哮喘患儿的C-ACT/ACT评分较治疗前均显著升高(P<0.05);GG型与GC型、CC型哮喘患儿治疗后的C-ACT/ACT评分比较差异均有统计学意义(P<0.05)。rs7701443位点3种基因型哮喘患儿C-ACT/ACT评分较治疗前均有显著升高(P<0.05),但治疗后3种基因型的C-ACT/ACT评分差异无统计学意义(P>0.05)。经ICS治疗后,rs41423247位点GG型、GC型哮喘患儿的各项肺功能指标较治疗前均有显著改善(P<0.05),而CC型哮喘患儿只有MMEF较治疗前有显著改善(P<0.05);经ICS治疗后,rs7701443位点3种基因型各项肺功能指标均较治疗前有显著改善(P<0.05)。结论NR3C1位点rs41423247、rs7701443均存在基因多态性,该研究未发现儿童哮喘患者与健康对照者中NR3C1位点rs41423247、rs7701443的基因多态性存在差异。儿童哮喘患者NR3C1位点rs41423247、rs7701443的不同基因型频率对ICS治疗效果存在差异。

Objective To investigate the correlation between single nucleotide polymorphism of corticosteroids receptor gene(NR3C1)and children with asthma and to analyze the efficacy of inhaled corticosteroid(ICS)treatment.Methods The study included a control group(100 healthy children)who participated in the physical examination and an asthma group(101 children with bronchial asthma)who were hospitalized in the General Hospital of the Northern Theater Command from October 2018 to October 2020.Genomic DNA was extracted from peripheral blood samples of all enrolled subjects and then the polymorphism of the glucocorticoid receptor gene locus of NR3C1 was analyzed using SNaPshot SNP gene detection technology.The comparisons of allele frequency in rs41423247、rs7701443 between two groups were performed and the treatment effects of ICS in the asthma group were evaluated at the 12th week of treatment.Results The frequencies of GG,GC,and CC genotypes of rs41423247 locus of NR3C1 were 75.2%,21.8%,and 3.0%in the asthma group and 72.0%,24.0%,and 4.0%in the control group,respectively,and there were no statistically significant differences between the two groups(χ^(2)=0.333,P>0.05).The frequencies of GG,GA,and AA genotypes of rs7701443 locus of NR3C1 were 45.5%,39.6%,and 14.9%in the asthma group and 56.0%,31.0%,and 13.0%in the control group,respectively,and there were no statistically significant differences between the two groups(χ^(2)=2.259,P>0.05).After ICS treatment,the C-ACT/ACT scores were not significantly improved in children with CC genotypes at rs41423247 locus(P>0.05),while children with GG and GC genotypes were obviously improved(P<0.05).The scores of C-ACT/ACT showed obvious differences among three genotypes of rs41423247 locus after treatment with ICS(P<0.05).The C-ACT/ACT scores of all were significantly improved in children with GG,GA,or AA genotypes at rs7701443 locus after treatment with ICS(P<0.05),while there was no significant difference among those three genotypes(P>0.05).Significantly improved pulmonary function following ICS treatment in children with asthma was observed in GG and GC genotypes of rs41423247 locus of NR3C1(P<0.05),while only MMEF was improved in CC genotype(P<0.05).Meanwhile,those pulmonary function indexes were improved in all genotypes of rs7701443 after treatment with ICS(P<0.05).Conclusion Both rs41423247 and rs7701443 locus at NR3C1 gene have polymorphisms.But there were no significant differences in the polymorphism of rs41423247 and rs7701443 locus of NR3C1 between the asthma group and the control group.Different genotype frequencies of rs41423247 and rs7701443 at NR3C1 locus in children with asthma have different effects on ICS treatment.