ADCY9基因的rs2601796变异与重症哮喘和支气管扩张剂低反应性相关
2023/10/25
摘要
背景：哮喘是一种由遗传和环境因素共同作用引起的呼吸系统疾病。腺苷酸环化酶9 (ADCY9)产生环磷酸腺苷酸(cAMP)，cAMP是参与支气管扩张和免疫调节反应的重要介质。
目的：本研究的目的是研究ADCY9基因中的rs2601796和rs2532019变异是否与哮喘和肺功能相关。
方法：这项研究包括1052名受试者。采用PLINK 1.9进行Logistic回归，经性别、年龄、BMI、吸烟和主成分调整。使用支气管扩张剂前后FEV1差异百分比评估支气管扩张剂反应性。基因表达的计算机分析在GTEx Portal中进行。
结果：变异rs2601796 (AA/AG基因型)与哮喘严重程度呈正相关(OR: 1.60 IC95%:1.08-2.39)，与重症哮喘患者梗阻呈正相关(OR: 3.10, IC95%:1.11-8.62)。重症哮喘和rs2601796 AA/AG基因型患者对支气管扩张剂的反应性较低，肺和全血中ADCY9的表达也较低。变异rs2532019 (TT/GT基因型)也下调ADCY9基因的表达，但与所研究的表型无显著相关性。
结论：因此，ADCY9的变异与更糟糕的哮喘结果相关，包括对支气管扩张剂的反应较低，可能是由于其基因表达率受到影响。这种变异可能在未来有助于哮喘患者的个性化管理。
The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response
H. M. P. Teixeira, A. A. Cruz, T. S. Jesus, M. B. R. de Santana, M. S. Jesus, R. Tugores, et al.
Abstract
BACKGROUND: Asthma is a respiratory disease caused by the interaction of genetic and environmental factors. The adenylyl cyclase type 9 (ADCY9) enzyme produces the cyclic-adenosinemonophosphate (cAMP), important mediator involved in bronchodilation and immunomodulatory response.
OBJECTIVE: The aim of this study was to investigate if rs2601796 and rs2532019 variants in the ADCY9 gene are associated with asthma and lung function.
METHOD：The study comprised 1,052 subjects. Logistic regressions were done using PLINK 1.9 adjusted by sex, age, BMI, smoke and principal components. Bronchodilator responsiveness was assessed using the percentage of difference in FEV1 before and after the bronchodilator use. The in silico analysis for gene expression was performed in the GTEx Portal.
RESULT:The variant rs2601796 (AA/AG genotype) was positively associated with asthma severity (OR: 1.60 IC95%: 1.08-2.39) and with obstruction in individuals with severe asthma (OR: 3.10, IC95%: 1.11-8.62). Individuals with severe asthma and the AA/AG genotype of rs2601796 had less responsiveness to bronchodilators and also a lower expression of ADCY9 in lung and whole blood. The variant rs2532019 (TT/GT genotype) also downregulated the ADCY9 gene expression, but no significant association with the studied phenotypes was found.
CONCLUSION:Thus, the variant in ADCY9 was associated with worse asthma outcomes, including a lower response to bronchodilators, likely due to the impact on its gene expression rate. This variant may be useful in the future to assist in personalized management of patients with asthma.
背景：哮喘是一种由遗传和环境因素共同作用引起的呼吸系统疾病。腺苷酸环化酶9 (ADCY9)产生环磷酸腺苷酸(cAMP)，cAMP是参与支气管扩张和免疫调节反应的重要介质。
目的：本研究的目的是研究ADCY9基因中的rs2601796和rs2532019变异是否与哮喘和肺功能相关。
方法：这项研究包括1052名受试者。采用PLINK 1.9进行Logistic回归，经性别、年龄、BMI、吸烟和主成分调整。使用支气管扩张剂前后FEV1差异百分比评估支气管扩张剂反应性。基因表达的计算机分析在GTEx Portal中进行。
结果：变异rs2601796 (AA/AG基因型)与哮喘严重程度呈正相关(OR: 1.60 IC95%:1.08-2.39)，与重症哮喘患者梗阻呈正相关(OR: 3.10, IC95%:1.11-8.62)。重症哮喘和rs2601796 AA/AG基因型患者对支气管扩张剂的反应性较低，肺和全血中ADCY9的表达也较低。变异rs2532019 (TT/GT基因型)也下调ADCY9基因的表达，但与所研究的表型无显著相关性。
结论：因此，ADCY9的变异与更糟糕的哮喘结果相关，包括对支气管扩张剂的反应较低，可能是由于其基因表达率受到影响。这种变异可能在未来有助于哮喘患者的个性化管理。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Gene 2023 Vol. 886 DOI: ARTN 14771410.1016/j.gene.2023.147714）
（Gene 2023 Vol. 886 DOI: ARTN 14771410.1016/j.gene.2023.147714）
The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response
H. M. P. Teixeira, A. A. Cruz, T. S. Jesus, M. B. R. de Santana, M. S. Jesus, R. Tugores, et al.
Abstract
BACKGROUND: Asthma is a respiratory disease caused by the interaction of genetic and environmental factors. The adenylyl cyclase type 9 (ADCY9) enzyme produces the cyclic-adenosinemonophosphate (cAMP), important mediator involved in bronchodilation and immunomodulatory response.
OBJECTIVE: The aim of this study was to investigate if rs2601796 and rs2532019 variants in the ADCY9 gene are associated with asthma and lung function.
METHOD：The study comprised 1,052 subjects. Logistic regressions were done using PLINK 1.9 adjusted by sex, age, BMI, smoke and principal components. Bronchodilator responsiveness was assessed using the percentage of difference in FEV1 before and after the bronchodilator use. The in silico analysis for gene expression was performed in the GTEx Portal.
RESULT:The variant rs2601796 (AA/AG genotype) was positively associated with asthma severity (OR: 1.60 IC95%: 1.08-2.39) and with obstruction in individuals with severe asthma (OR: 3.10, IC95%: 1.11-8.62). Individuals with severe asthma and the AA/AG genotype of rs2601796 had less responsiveness to bronchodilators and also a lower expression of ADCY9 in lung and whole blood. The variant rs2532019 (TT/GT genotype) also downregulated the ADCY9 gene expression, but no significant association with the studied phenotypes was found.
CONCLUSION:Thus, the variant in ADCY9 was associated with worse asthma outcomes, including a lower response to bronchodilators, likely due to the impact on its gene expression rate. This variant may be useful in the future to assist in personalized management of patients with asthma.
上一篇：
重度哮喘患者的烟草暴露和生物治疗的疗效:来自丹麦重度哮喘登记的一项全国性研究
下一篇：
人类巨噬细胞迁移抑制因子增强了在过敏性哮喘临床相关模型中间充质干细胞的疗效
