FKBP5基因多态性与小儿支气管哮喘易感性及糖皮质激素疗效的关系研究

Relationship Between FKBP5 Gene Polymorphism and Bronchial Asthma Susceptibility and Glucocorticoid Efficacy in Children

目的探讨FK506结合蛋白5(FK506-binding protein 5,FKBP5)基因多态性与小儿支气管哮喘易感性及糖皮质激素(glucocorticoid,GC)疗效的关系。方法选取2021-04/2023-04月作者医院收治的120例支气管哮喘患儿作为研究对象(哮喘组)。另外将同时期来作者医院进行体检的150例健康儿童作为健康组。根据GC疗效不同将支气管哮喘患儿分为良好组(n=92)和不良组(n=28)。采用限制性片段长度多态性聚合酶链反应(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)技术鉴定FKBP5基因rs4713916位点基因分型。采用Hardy-Weinberg遗传平衡度检验对样本代表性进行评估。结果健康组和哮喘组FKBP5基因rs4713916位点基因型符合Hardy-Weinberg遗传平衡定律,样本具有代表性(P>0.05)。健康组FKBP5基因rs4713916位点TT(7.33%vs.18.33%)、TC(34.67%vs.37.50%)、CC(58.00%vs.44.17%)基因型频率和T(24.67%vs.37.08%)、C(75.33%vs.62.92%)等位基因频率与哮喘组比较差异有统计学意义(P均<0.05)。良好组FKBP5基因rs4713916位点TT(7.61%vs.53.57%)、TC(40.22%vs.28.57%)、CC(52.17%vs.17.86%)基因型频率和T(27.72%vs.67.86%)、C(72.28%vs.32.14%)等位基因频率与不良组比较差异有统计学意义(P均<0.05)。FKBP5基因rs4713916位点TT基因型患儿治疗前后第1秒用力呼气容积(forced expiratory volume in one second,FEV1)、用力肺活量(forced vital capacity,FVC)、FEV1/FVC的差值低于TC、CC基因型患儿,且TC基因型低于CC基因型(P均<0.05)。结论FKBP5基因rs4713916位点多态性与小儿支气管哮喘易感风险和GC疗效有关,且携带TT基因型患儿对GC治疗的敏感性更差。

Objective To explore the relationship between FK506-binding protein 5(FKBP5)gene polymorphism and susceptibility to bronchial asthma and glucocorticoid(GC)efficacy in children.Methods A total of 120 children with bronchial asthma admitted to author′s hospital from April 2021 to April 2023 were prospectively selected as the subjects of this study(asthma group).In addition,150 healthy children who came to author′s hospital for physical examination during the same period were selected as the healthy group.The children were divided into good group(n=92)and poor group(n=28)according to GC efficacy.Genotype of rs4713916 locus of FKBP5 gene was identified by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Hardy-Weinberg genetic balance test was used to evaluate the representativeness of the samples.Results The genotype of rs4713916 locus of FKBP5 gene in the healthy group and asthma group was in accordance with the Hardy-Weinberg genetic equilibrium law,and the samples were representative(P>0.05).In healthy group,TT(7.33%vs.18.33%),TC(34.67%vs.37.50%),CC(58.00%vs.44.17%)genotype frequencies of rs4713916 of FKBP5 gene and T(24.67%vs.37.08%),C(75.33%vs.62.92%)allele frequency was significantly different from that of asthma group(all P<0.05).The genotype frequencies of rs4713916 TT(7.61%vs.53.57%),TC(40.22%vs.28.57%),CC(52.17%vs.17.86%)and T(27.72%vs.67.86%),C(72.28%vs.32.14%)in the good group allele frequency was significantly different from that of the poor group(all P<0.05).The difference values of forced expiratory volume in one second(FEV_1),forced vital capacity(FVC)and FEV_1/FVC in TT genotype with rs4713916 of FKBP5 gene before and after treatment were lower than those of TC and CC genotype,and TC genotype was lower than CC genotype(all P<0.05).Conclusion rs4713916 polymorphism of FKBP5 gene is associated with the susceptibility risk of bronchial asthma and GC efficacy in children,and children with TT genotype are less sensitive to GC treatment.