胞浆型磷脂酶A2多态性与儿童支气管哮喘发生及孟鲁司特疗效的相关性

目的 探究胞浆型磷脂酶A2（PLA2G4）基因rs932476位点多态性与儿童支气管哮喘发生及白三烯受体拮抗剂孟鲁司特治疗反应性的相关性。方法 收集支气管哮喘患儿128例为病例组，100例健康儿童为对照组。比较两组儿童PLA2G4基因rs932476位点基因型及等位基因分布。病例组患儿采用常规治疗+孟鲁司特方案治疗2个月。比较病例组患儿治疗前后血清白三烯B4（LTB4）及炎性因子白细胞介素-4（IL-4）、免疫球蛋白E（IgE）和γ-干扰素（IFN-γ）、肺功能和呼出气一氧化氮（FeNO）的水平。结果 PLA2G4基因rs932476位点基因型及等位基因频率在病例组和对照组之间及不同严重程度哮喘组之间的分布差异均无统计学意义（P > 0.05）。治疗后AA型患儿总有效率高于GG型，差异有统计学意义。与治疗前相比，治疗后各基因型患儿血清IgE和IL-4水平降低，IFN-γ水平升高（P < 0.05）。治疗后GG型患儿血清IL-4水平高于AA型，IFN-γ的水平低于AA型。治疗后，各基因型患儿的肺功能参数升高，其中AA型患儿显著高于GG型；而FeNO水平治疗后明显下降，其中AA型患儿明显低于GG型。病例组治疗前血清LTB4水平明显高于对照组（P < 0.05）。治疗后病例组血清LTB4水平明显降低（P < 0.05），其中GG基因型患儿LTB4水平高于AA型（P < 0.05）。结论 PLA2G4基因rs932476位点多态性与儿童支气管哮喘的易感性及病情严重程度无关，但对白三烯受体拮抗剂孟鲁司特的疗效有一定的影响，其机制可能与影响LTB4水平有关。

Association of cytoplasmic phospholipase A2 gene polymorphism with bronchial asthma and response to montelukast in children

Objective To study the association of cytoplasmic phospholipase A2 (PLA2G4) rs932476 polymorphism with the development of bronchial asthma and the response to montelukast, a leukotriene receptor antagonist, in children. Methods A total of 128 children with bronchial asthma were enrolled as case group, and 100 healthy children were enrolled as control group. The genotype and allele frequencies of PLA2G4 rs932476 were compared between the two groups. The children in the case group were administered with montelukast except routine treatment for 2 months, and the changes in serum levels of leukotriene B4 (LTB4), interleukin-4 (IL-4), immunoglobulin E (IgE), and interferon gamma (IFN-γ), pulmonary function and fractional exhaled nitric oxide (FeNO) after treatment were observed. Results There were no significant differences in the genotype and allele frequencies of PLA2G4 rs932476 between the case and control groups, as well as between the groups with different severities of asthma (P > 0.05). After treatment, the children with AA genotype had a significantly higher overall response rate than those with GG genotype. After treatment, the case group had significant reductions in the serum levels of IgE and IL-4 and a significant increase in the level of IFN-γ (P < 0.05). After treatment, the children with GG genotype had a higher serum level of IL-4 and a lower level of IFN-γ than those with AA genotype. After treatment, the case group had significant increases in pulmonary function parameters, and the children with AA genotype had significantly higher parameters than those with GG genotype. The case group had a significant reduction in the level of FeNO, and the children with AA genotype had a significantly lower level than those with GG genotype after treatment. The case group had a significantly higher serum level of LTB4 than the control group before treatment (P < 0.05). After treatment the case group had a significant reduction in the serum level of LTB4 (P < 0.05). The children with GG genotype had a significantly higher level of LTB4 than those with AA genotype after treatment (P < 0.05). Conclusions PLA2G4 rs932476 polymorphism is not associated with the susceptibility and severity of bronchial asthma in children, but it may has certain influence on children's response to the leukotriene receptor antagonist montelukast, possibly by affecting the level of LTB4.