Gupta Sarika, Awasthi Shally
Department of Pediatrics, C.S.M.M.U., Lucknow, Uttar Pradesh, India.
Indian J Hum Genet. 2010 Sep;16(3):111-8. doi: 10.4103/0971-6866.73398.
Asthma is a complex disease with multiple genetic and environmental factors contributing to it. A component of this complexity is a highly variable response to pharmacological therapy. Pharmacogenomics is the study of the role of genetic determinants in the variable response to therapy. A number of examples of possible pharmacogenomic approaches that may prove of value in the management of asthma are discussed below.
A search of PubMed, Google scholar, E-Medicine, BMJ and Mbase was done using the key words "pharmacogenomics of asthma", "pharmacogenomics of β-agonist, glucocorticoids, leukotriene modifiers, theophylline, muscarinic antagonists in asthma".
Presently, there are limited examples of gene polymorphism that can influence response to asthma therapy. Polymorphisms that alter response to asthma therapy include Arg16Gly, Gln27Glu, Thr164Ile for β-agonist receptor, polymorphism of glucocorticoid receptor gene, CRHR1 variants and polymorphism of LTC4S, ALOX5. Polymorphic variants of muscarinic receptors, PDE4 and CYP450 gene variants.
It was concluded that genetic variation can improve the response to asthma therapy. However, no gene polymorphism has been associated with consistent results in different populations. Therefore, asthma pharmacogenomic studies in different populations with a large number of subjects are required to make possible tailoring the asthma therapy according to the genetic characteristic of individual patient.
哮喘是一种复杂的疾病，由多种遗传和环境因素共同导致。这种复杂性的一个方面是对药物治疗的反应高度可变。药物基因组学是研究遗传决定因素在治疗反应变异性中的作用。以下讨论了一些可能在哮喘管理中具有价值的药物基因组学方法实例。
使用关键词“哮喘的药物基因组学”“哮喘中β受体激动剂、糖皮质激素、白三烯调节剂、茶碱、毒蕈碱拮抗剂的药物基因组学”在PubMed、谷歌学术、E-Medicine、英国医学杂志和Mbase上进行了检索。
目前，能够影响哮喘治疗反应的基因多态性实例有限。改变哮喘治疗反应的多态性包括β受体激动剂受体的Arg16Gly、Gln27Glu、Thr164Ile，糖皮质激素受体基因多态性、CRHR1变异体以及LTC4S、ALOX5的多态性。毒蕈碱受体的多态性变体、PDE4和CYP450基因变体。
得出的结论是，基因变异可以改善哮喘治疗反应。然而，没有一种基因多态性在不同人群中都能产生一致的结果。因此，需要在不同人群中开展大量受试者参与的哮喘药物基因组学研究，以便根据个体患者的遗传特征定制哮喘治疗方案。
