药物-基因组学与哮喘个体化诊疗的研究

Study of pharmaco-genomics for individualized diagnosis and treatment of asthma

目的检测与哮喘药物疗效相关基因的SNP基因型,分析差异SNP不同基因型与患者临床特征及生物标志物的相关性,探讨SNP筛查在哮喘患者个体化诊疗中的价值。方法入选98例哮喘患者,选择542例健康人作对照,利用MassARRAY质谱测序方法检测患者9个基因的10个SNP位点基因型,通过病例-对照研究寻找差异SNP并分析不同基因型与患者临床特征及生物标志物的相关性,结合基因检测指导患者个体化诊疗。结果按照检出纯合子风险基因为阳性标准,该研究共检出58例阳性患者(占比59.2%)。哮喘患者CRHR1 rs1876828 T等位基因的发生频次显著高于对照组(P<0.05);FCER2 rs28364072位点A等位基因的发生频次显著低于对照组(P<0.05);与FCER2 rs28364072等位基因为AA+AG的患者比较,等位基因为GG型的患者哮喘未控制比例、重症哮喘患者比例更高、FeNO更低(P<0.05);利用药物基因组学指导部分患者个体化用药取得了满意疗效。结论本研究10个SNP位点组合有望开发为指导哮喘患者用药的生物标志物,为患者个体化诊疗方案的制订提供依据。

Objective To detect the SNP genotypes of genes related to the efficacy of asthma drugs,to analyze the correlation between different SNP genotypes and the clinical characteristics and biomarkers of patients,and to explore the value of SNP screening in individualized diagnosis and treatment of asthma patients.Methods 98 patients with asthma were enrolled,and 542 healthy people were selected as controls.MassARRAY mass spectrometry sequencing method was used to detect the genotypes of 10 SNP loci of 9 genes in patients,and the case-control study was used to find the differential SNPs and analyze different genotypes and the correlation biomarkers.Combined with genetic testing to guide individualized diagnosis and treatment of patients.Results According to the positive standard of detecting homozygous risk genes,a total of 58 positive patients(59.2%)were detected in this study.The occurrence frequency of CRHR1 rs1876828 T allele in asthma patients was significantly higher than that in the control group(P<0.05);the occurrence frequency of FCER2 rs28364072 locus A allele was significantly lower than that in the control group(P<0.05).Compared with patients whose FCER2 rs28364072 allele was AA+AG,the proportion of patients with GG allele was uncontrolled,the proportion of severe asthma patients was higher,and FeNO was lower(P<0.05);The use of pharmacogenomics to guide the individualized medication of some patients has achieved satisfactory results.Conclusion The combination of 10 SNP loci in this study is expected to be developed as a biomarker to guide the medication of asthma patients,and provide a basis for the formulation of individualized diagnosis and treatment plans for patients.