Suppr超能文献

南印度哮喘患者中ADRB2(Arg16Gly)基因变异与易感性、药物遗传学反应及疾病严重程度的分析

Analysis of ADRB2 (Arg16Gly) Gene Variant with Susceptibility, Pharmacogenetic Response and Disease Severity in South Indian Asthmatics.

作者信息

Bandaru Srinivas, Akka Jyothy, Marri Vijaya Kumar, Alvala Mallika, Ponnala Deepika, Mundluru Hema Prasad

机构信息

National Institute of Pharmaceutical Education and Research, Hyderabad, 500 037, India.

Department of Toxicology, Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad, 500 016, India.

出版信息

Inflammation. 2015 Dec;38(6):2146-55. doi: 10.1007/s10753-015-0197-y.

Abstract

β2-Adrenergic receptor (β2-AR) plays a crucial role in asthma pathophysiology by regulating, processes of the lung function, and clinical response to bronchodilators. The +46G>A- Gly16Arg polymorphism in the gene encoding β2 adrenergic receptor (ADRB2) has been associated with receptor non-responsiveness after β2-agonist exposure. In the present study, we sought to evaluate the possible association of Gly16Arg polymorphism with asthma susceptibility, pharmacogenetic response to Salbutamol, and varying degrees of disease severity. Three hundred ninety-eight clinically diagnosed patients and 456 healthy controls were enrolled for the study. Patients were classified into severity classes according to Global Initiative for Asthma guidelines. To assess bronchodilator response, spirometry was performed before and 15 min after Salbutamol (200 μg) delivery. Responders to Salbutamol were categorized if percentage reversibility was greater than or equal to 12% in them, while those showing reversibility less than 12% were classified as non-responders. Genotyping was carried out by ARMS-PCR technique. Statistical methods were applied to test for the significance of the results. In the present study, there was lack of significant association of polymorphism with disease susceptibility as well as with bronchodilator response. The polymorphism was not associated with mild and moderate asthma subtypes; however, there was a notable association with severe asthma subtype. In addition, the polymorphism was associated with severe asthma compared to subtypes of mild and moderate asthma combined. In a South Indian population, the ADRB2 Arg/Gly may not form a susceptible variant to develop asthma nor can be a standard predictive marker to bronchodilator response; nevertheless, the patterns in asthma severity can be predicted by analyzing this variant.

摘要

β2肾上腺素能受体(β2-AR)通过调节肺功能过程和对支气管扩张剂的临床反应,在哮喘病理生理学中发挥关键作用。β2肾上腺素能受体(ADRB2)编码基因中的+46G>A - Gly16Arg多态性与β2激动剂暴露后受体无反应性有关。在本研究中,我们试图评估Gly16Arg多态性与哮喘易感性、对沙丁胺醇的药物遗传学反应以及不同程度疾病严重程度之间的可能关联。本研究纳入了398例临床诊断患者和456例健康对照。根据全球哮喘防治创议指南将患者分为不同严重程度等级。为评估支气管扩张剂反应,在给予沙丁胺醇(200μg)前及给药后15分钟进行肺功能测定。沙丁胺醇反应者若其可逆百分比大于或等于12%则被分类为反应者,而可逆性小于12%者被分类为无反应者。采用扩增阻滞突变系统聚合酶链反应(ARMS-PCR)技术进行基因分型。应用统计方法检验结果的显著性。在本研究中,多态性与疾病易感性以及支气管扩张剂反应之间缺乏显著关联。该多态性与轻度和中度哮喘亚型无关;然而,与重度哮喘亚型存在显著关联。此外,与轻度和中度哮喘亚型合并相比,该多态性与重度哮喘相关。在南印度人群中,ADRB2 Arg/Gly可能不是发生哮喘的易感变异,也不能作为支气管扩张剂反应的标准预测标志物;尽管如此,通过分析该变异可以预测哮喘严重程度模式。

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验