哮喘相关药物基因组学的研究进展

摘要/Abstract

摘要： 目的：了解基于哮喘相关药物治疗的基因组学研究进展，以期为临床个体化用药提供参考。方法：查阅近年来国内外相关文献，就ADRB2基因、CRHR1基因、ORMDL3基因和ALOX5基因的基因多态性对药效影响的研究进展进行归纳和总结。结果：ADRB2基因Arg16Arg患者定期规律服用短效的β2-受体激动剂（SABA）出现肺功能指标下降和哮喘病情加重的现象；长效的β2-受体激动剂（LABA）在成人和儿童中的治疗效果截然相反，在成人哮喘患者中基因型Arg16Arg、Arg16Gly和Gly16Gly的肺功能均得到了改善，而在儿童中Arg16Arg基因型则使哮喘急性加重的风险增加。CRHR1基因rs242941位点GT基因型和TT基因型更易引起哮喘急性发作，各基因型患者使用吸入性糖皮质激素（ICSs）治疗后，气道高反应性均明显改善。ORMDL3基因rs7216389位点野生纯合子TT是哮喘的保护位点基因，而突变纯合子CC是哮喘的敏感基因，已有研究表明ICSs可能通过下调ORMDL3的mRNA表达，改善气道重塑。患者使用白三烯调节剂（LTMs）应答后，ALOX5（rs2115819）基因中CC和CT相比TT哮喘恶化发生率更低且改善第一秒呼气容积（FEV1）更明显。结论：随着哮喘相关药物基因组学的不断发展和完善，其更多明确的功能基因将推动哮喘个体化给药的实现，提高哮喘患者用药的安全性和有效性。

Abstract: Objective:To understand the progress of genomics research based on asthma-related drug therapies in order to provide reference for individualized drug use in clinic.Methods: Check the relevant documents in recent years at home and abroad. The research progress on the effects of ADRB2 gene, CRHR1 gene, ORMDL3 gene and ALOX5 gene polymorphism on drug efficacy was summarized and summarized. Results: Patients with Arg16 Arg regularly suffered from a decline in lung function and exacerbation of asthma due to regular short-acting β2-agonists (SABA). The long-acting beta2-agonists (LABA) have an opposite therapeutic effect in adults and children. Lung function of genotypes Arg16Arg, Arg16Gly, and Gly16Gly has been improved in adult asthmatic patients. However, the Arg16Arg genotype in children increases the risk of acute asthma exacerbations. CRHR1 gene rs242941 GT genotype and TT genotype are more likely to cause acute asthma attacks. However, all patients with genotypes treated with inhaled glucocorticoids (ICSs) had significantly improved airway hyperresponsiveness. ORMDL3 gene rs7216389 locus wild homozygous TT is a protective gene for asthma and homozygous mutant CC is a sensitive gene for asthma. Studies have shown that ICS may improve airway remodeling by downregulating ORMDL3 mRNA expression. After patients responded with leukotriene modulators (LTMs), CC and CT in the ALOX5 (rs2115819) gene had a lower incidence of asthma exacerbations than TT and improved first-second expiratory volume (FEV1) was more pronounced. Conclusion: With the continuous development and improvement of asthma-related drug genomics, more specific functional genes will promote the realization of individualized asthma administration to improve the safety and effectiveness of asthma patients.

廉悦. 哮喘相关药物基因组学的研究进展[J]. .

lianyue. Advances in Asthma-related Pharmacogenomics[J]. .

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