MTHFR基因多态性与儿童支气管哮喘易感性及糖皮质激素疗效的相关性

Relationship between MTHFR gene polymorphism and susceptibility to bronchial asthma and glucocorticoid efficacy in children

摘要:

目的 探讨亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase，MTHFR）基因多态性与儿童支气管哮喘易感性及糖皮质激素（glucocorticoid，GC）疗效的相关性。 方法 选取2018年6月至2020年12月住院治疗的儿童支气管哮喘患儿173例为观察组，均接受GC雾化吸入治疗，连续3个月。选取同期体检的健康儿童178例为对照组。采用PCR检测两组受试儿MTHFR基因C677T位点的基因型，分析两组基因型分布差异性；比较观察组不同基因型患儿治疗前后血清免疫球蛋白E、白细胞介素-8（interleukin-8，IL-8）、白三烯B4（leukotriene B4，LTB4）水平，肺功能指标差异及临床疗效差异。 结果 与对照组相比，观察组TT基因型及T等位基因频率均显著升高（P<0.001）；TT/CT基因型及T等位基因是支气管哮喘易感性的独立危险因素（OR分别为6.615、7.055，P<0.001）。GC治疗后3种基因型患儿免疫球蛋白E、IL-8和LTB4水平较治疗前显著降低，第1秒用力呼气容积（forced expiratory volume in 1 second，FEV1）、用力肺活量（forced vital capacity，FVC）、FEV1/FVC%较治疗前显著升高（P<0.001）；TT基因型患儿IL-8和LTB4水平显著低于CC基因型患儿，LTB4水平明显低于CT基因型患儿，TT基因型患儿FVC明显高于CT基因型患儿，FEV1/FVC%显著高于CC基因型患儿（P<0.05）；治疗后3种基因型患儿临床GC治疗疗效比较差异有统计学意义，其中TT基因型患儿GC疗效良好比例显著高于CC基因型患儿（P<0.05），且TT基因型是GC疗效良好的独立影响因素（OR=2.111，P=0.018）。 结论 MTHFR基因多态性与儿童哮喘易感性及GC疗效相关，携带TT/CT基因型儿童支气管哮喘发病风险更高，TT基因型对GC治疗具有更高的敏感性。

Abstract:

Objective To study the association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with susceptibility to bronchial asthma and glucocorticoid (GC) efficacy in children. Methods A total of 173 children with bronchial asthma who were hospitalized between June 2018 and December 2020 were selected as the observation group. The children received aerosol inhalation of GC for three consecutive months. A total of 178 healthy children who underwent physical examination during the same period were selected as the control group. PCR was used to detect the genotypes of the MTHFR C677T for the two groups. The differences in genotype distribution between the two groups were analyzed. Children with different genotypes in the observation group were compared in terms of immunoglobulin E (IgE), interleukin-8 (IL-8), leukotriene B4 (LTB4), lung function, and clinical outcome before and after treatment. Results TT genotype and T allele were significantly more frequent in the observation group than in the control group (P<0.001). TT/CT genotypes and T allele were independent risk factors for bronchial asthma (OR=6.615 and 7.055 respectively; P<0.001). After GC treatment, the children with CC, CT or TT genotypes experienced significantly decreased levels of IgE, IL-8, and LTB4 and significantly increased forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio (P<0.001). The children with TT genotype showed significantly lower levels of IL-8 and LTB4 than those with CC genotype, a significantly lower level of LTB4 than those with CT genotype, significantly higher FVC than those with CT genotype, and a significantly higher FEV1/FVC ratio than those with CC genotype (P<0.05). The children with TT genotype had better GC efficacy compared with those with CC genotype (P<0.05). TT genotype was an independent factor for good GC efficacy (OR=2.111, P=0.018). Conclusions MTHFR gene polymorphism is associated with asthma susceptibility and GC efficacy in children. Children carrying TT/CT genotypes have a higher risk of developing asthma, and those with TT genotype are more sensitive to GC treatment.