Relationship Between Asthma Control Level And Pharmacogenetic SNP In Children

Objective: This article uses a prospective study to analyze the influencing factors of clinical control efficacy of initial treatment plan in children with asthma,selectively detects single nucleotide polymorphisms(SNPs)of budesonide and montelukast sodium drug genes,explores the relationship between the clinical control effect of drugs and the pharmacogenetic SNP and provides possible evidence and feasible guidance for initial anti-inflammatory treatment in children with asthma.Method: Part ?: A total of 185 infants with wheezing in the Department of Respiratory Medicine and Infectious Diseases of Tianjin Children's Hospital from August 2017 to January 2018 were selected.According to the inclusion criteria and exclusion criteria,a total of 60 subjects were included.The inclusion criteria:(1)Age ? 5 years old,API index is positive;or a severe asthmatic attack confirmed by the doctor,anti-asthma treatment is effective;(2)Inhaled or nasal corticosteroids have not been used in the past 2 months;(3)No topical or systemic corticosteroid treatment was performed within 3 months.Exclusion criteria: Congenital heart and lung disease,primary immunodeficiency disease,gastroesophageal reflux disease and other diseases that can cause repeated wheezing in infants.These 60 subjects were divided into well-controlled group and poorly controlled group according to the control of wheezing after 3 months of follow-up.Compare general information(including gender,living environment,feeding style,only child,mode of production,family history,history of passive smoking,history of eczema,history of preterm birth,and use of ICS during hospitalization)and laboratory tests(FeNO,IgE,lung function)between the two groups.Part ?: 12 subjects in 60 subjects were randomly selected according to the ratio of 5:1.Real time PCR was used to determine the genotypes of six SNPs(rs730012,rs2115819,rs12422149,rs2660845,rs1876828,rs37973)of budesonide and montelukast sodium receptor genes,and the clinical control and genotype were combined for analysis.Result: Part ?: By comparing the general data of children with well control and poorcontrol,including gender,living environment,feeding style,only child,mode of production,family history,history of passive smoking,history of eczema,history of premature birth,etc.,the difference was not statistically significant(P>0.05).There was no significant difference in FeNO,IgE and lung function between the two groups(P>0.05).Inhalation of high-dose budesonide suspension(1 mg q8h)was higher in the poorly controlled group than in the well-controlled group(P<0.01).Part ?: The second part was obtained from 12 cases of genetic test results and follow-up control: 7 children with good control,including children numbered 3,4,6,7,9,10,and 11;children 3 and 7 regularly used ICS and the gene detection budesonide receptor gene showed wild homozygous type.The Montelukast sodium receptor gene SNP detected by children 6,9,10,and 11 was different,and the budesonide receptor SNP was the same.Both of them used ICS and montelukast sodium,which had similar clinical effects.In the 4th child,there was a mutation in the SNP site of montelukast sodium,and the budesonide receptor gene showed homozygous wild type,which was mainly treated with ICS.Five children with poor control were numbered 1,2,5,8,and 12.Among the children with Wheezing No.1,there were mutations of montelukast sodium receptor rs2660845 and budesonide receptor rs37973 SNP,and rs37973 showed homozygous GG,and ICS and montelukast sodium were used irregularly.In children with Wheezing No.2,there were 4 SNP detection site mutations of montelukast sodium the main drug used was montelukast sodium.Both children with 5 and 8 had mutations in the SNP site of montelukast sodium,and the genotypes were the same.Conclusion: 1.The pharmacogenetic SNP of asthmatic children is an influential factor in the efficacy of the drug.2.Children with poor initial control of asthma in children can guide clinical selection and optimize treatment plan through pharmacogenetics.3.There is no exact correlation between the montelukast sodium receptor gene polymorphism and the efficacy of children with asthma.