哮喘儿童白三烯受体调节剂临床疗效与白三烯C4合成酶及5-脂氧化酶基因的相关性

The relationship between LTC4S, ALOX5 genetic polymorphism and clinical efficacy of leukotriene receptor modulators in children with asthma

目的探讨白三烯C4合成酶(LTC4S)与5-脂氧化酶(ALOX5)基因多态性与白三烯受体拮抗剂临床疗效的关系。方法 2011年6月至2013年6月门诊72例中度持续哮喘患儿分为两组,分别予吸入型糖皮质激素激素(ICS)、ICS联合白三烯受体拮抗剂(LTRA)治疗12周,然后交叉治疗12周;采用聚合酶链反应—限制性片段长度多态性方法(PCRRFLP),对LTC4S RS730012、ALOX5 RS2115819位点进行基因分型;分析患儿治疗前后肺功能及儿童哮喘控制测试问卷(C-ACT)评分与基因多态性的关系。结果经ICS联合LTRA治疗后,LTC4S RS730012基因组中的A/C、C/C基因型患儿的75%肺活量时的用力呼气流速(FEF75)改善率显著优于A/A型,差异均有统计学意义(P<0.01);A/A基因型患儿在治疗前后改善情况的差异无统计学意义。ICS联合LTRA治疗前后,ALOX5 RS2115819基因组中的不同基因型患儿间的肺功能指标差异无统计学意义(P>0.05)。结论 LTC4S RS730012不同基因型患儿在哮喘治疗后小气道功能改善有差异,与LTRA相关。

Objective To study the effect of genetic polymorphism of leukotriene C4 synthase （LTC4S） and 5-lipoxy-genase （ALOX5） on efifcacy of leukotriene receptor antagonist （LTRA） in children with moderate persistent asthma. Methods Seventy-two children with moderate persistent asthma who visited the out-patient clinic of Shanghai Children’s Medical. Center from June 2011 to June 2013 were divided into two groups, each of which ifrst had ICS or LTRA＋ICS for twelve weeks and then had the other for another twelve weeks. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） was used to assess the genetic polymorphism of LTC4S RS730012 and ALOX5 RS2115819. Pulmonary function, clinical symptoms and C-ACT score were evaluated before and after treatment. Results After the treatment with LTRA, 75%forced expiratory lfow （FEF75） was improved more signiifcantly in patients with A/C or C/C genotype at LTC4S （RS730012） locus than in patients with A/A genotype. After the treatment with LTRA＋ICS, there was no difference of pulmonary function among patients with different genotypes at ALOX5 （RS2115819）. Conclusions The SNP of LTC4S （RS730012） is associated with the efifcacy of montelukast in asthmatic patients because of the improvement of small airway function.