PLA2G4和ABCC1基因多态性与支气管哮喘患儿孟鲁司特疗效的研究

Study on the polymorphisms of PLA2G4 and ABCC1 genes and the efficacy of montelukast in children with bronchial asthma

摘要:

目的 探讨胞浆型磷脂酶A2（PLA2G4）基因和ATP结合盒亚家族C成员1（ABCC1）基因单核苷酸多态性（SNPs）与支气管哮喘儿童白三烯受体拮抗剂（LTRA）孟鲁司特疗效的关系。方法 选取2019年3月—2021年9月于中国人民解放军北部战区总医院诊治的121例哮喘患儿为研究对象，受试儿童均采用常规治疗+孟鲁司特方案治疗1个月。应用imLDR^TM技术检测受试儿童PLA2G4基因rs10157410、rs10489409、rs932476位点和ABCC1基因rs215066位点的SNPs，探究各位点不同基因型间治疗前后肺功能、炎症指标及哮喘症状控制水平分级的变化情况。结果 孟鲁司特治疗前后PLA2G4基因rs10157410、rs10489409、rs932476位点不同基因型间的肺功能指标比较，差异均无统计学意义（P >0.05）。孟鲁司特治疗后，PLA2G4基因rs10157410位点GC和GG基因型、rs10489409位点CT和TT基因型、rs932476位点GA和AA基因型及ABCC1基因rs215066位点的第1秒用力呼气容积占预计值百分比、第1秒用力呼气容积与用力肺活量比值、用力呼出50%和75%肺活量时的瞬时流量占预计值百分比均升高（P <0.05）。孟鲁司特治疗后，PLA2G4基因rs10489409位点CC基因型患儿嗜酸性粒细胞计数较治疗前改善不显著（P >0.05），PLA2G4、ABCC1基因各位点不同基因型的免疫球蛋白（IgE）、呼出气一氧化氮均较治疗前改善显著（P <0.05）。孟鲁司特治疗后，PLA2G4基因rs10157410位点GC基因型良好控制比例高于GG基因型，未控制低于GG基因型（P <0.05）；PLA2G4基因rs932476位点GA和AA基因型良好控制比例与GG基因型比较，差异有统计学意义（P <0.05）。Logistic回归分析结果显示，PLA2G4基因rs10157410位点GC基因型良好控制比例是GG基因型的5.639倍［O^R =5.639（95% CI：2.078，15.298）］，rs932476位点GG基因型良好控制比例是AA基因型的0.053倍［O^R =0.053（95% CI：0.006，0.430）］。结论 PLA2G4基因rs10157410位点GC基因型和rs932476位点AA基因型对孟鲁司特具有更好的敏感性。

Abstract:

Objective To investigate the correlation between single nucleotide polymorphisms (SNPs) of cytosolic phospholipase A2 (PLA2G4) gene and ATP-binding cassette subfamily C member 1 (ABCC1) gene and the efficacy of leukotriene receptor antagonists (LTRA) montelukast in children with bronchial asthma.Methods A total of 121 asthmatic children treated at the Northern Theater General Hospital of the People's Liberation Army from March 2019 to September 2021 were selected for the study. The children received routine treatment plus montelukast for one month. The imLDRTM technique was used to detect SNPs of PLA2G4 gene at rs10157410, rs10489409, rs932476 loci, and ABCC1 gene at rs215066 locus. Changes in lung function, inflammatory indicators, and asthma symptom control levels were explored among different genotypes at each locus before and after treatment.Results The comparison of lung function indicators among different genotypes of PLA2G4 gene at rs10157410, rs10489409, and rs932476 loci before and after montelukast treatment showed no significant differences (P > 0.05). After montelukast treatment, the percentage of predicted forced expiratory volume in 1 second (FEV₁), the ratio of FEV1 to forced vital capacity (FVC), and the percentage of predicted peak expiratory flow at 50% and 75% of vital capacity significantly increased for genotypes GC and GG at rs10157410 locus, CT and TT at rs10489409 locus, GA and AA at rs932476 locus, and for genotype CC at ABCC1 gene rs215066 locus (P < 0.05). After montelukast treatment, there was no significant improvement in eosinophil count in children with genotype CC at rs10489409 locus (P > 0.05), while immunoglobulin E (IgE) and exhaled nitric oxide levels significantly improved for different genotypes at PLA2G4 and ABCC1 gene loci compared to pre-treatment (P < 0.05). After montelukast treatment, the proportion of good control for genotype GC at rs10157410 locus was significantly higher than GG, and for genotypes GA and AA at rs932476 locus, the proportion of good control was significantly different from GG (P < 0.05). Logistic regression analysis showed that the proportion of good control for genotype GC at PLA2G4 gene rs10157410 locus was 5.639 times that of GG [O^R = 5.639 (95% CI: 2.078, 15.298) ], and the proportion of good control for genotype GG at rs932476 locus was 0.053 times that of AA [O^R = 0.053 (95% CI: 0.006, 0.430) ].Conclusion PLA2G4 gene rs10157410 genotype GC and rs932476 genotype AA have better sensitivity to the efficacy of montelukast.