药物基因组学和药物蛋白质组学杂志

抽象的

Novel Asthma Therapeutics: Insights from Whole-Genome Studies

Ting F Leung, Man F Tang, Hing Y Sy and Gary WK Wong

Asthma is characterized by recurrent and reversible airflow obstruction as well as bronchial hyper-responsiveness. Airway inflammation is central to asthma pathogenesis. Bronchodilators are advocated as rescue treatments for acute asthma symptoms, whereas anti-inflammatory drugs such as Inhaled Corticosteroids (ICS) are common controller therapies for chronic asthma. Leukotriene modifiers are widely prescribed alternatives to ICS. During the past several years, a number of pharmacogenomic studies adopting whole-genome arrays have identified novel gene targets that contribute to the heterogeneity in responses to these anti-asthma drugs. These gene chips contain dense probes
that capture either genotypes of single-nucleotide polymorphisms or the expression of genes across the entire human genome. Through these approaches, CLCA1, periostin, serpinB2, FKBP51, NFKB, GLCCI1 and T gene were reported to modulate ICS response in asthma patients whereas ARG1, CRHR2, SPATS2L and COL22A1were novel genes for bronchodilator responses. Some of these therapeutic targets were replicated in independent populations and/or supported by downstream in vitro and in vivo experiments on their functionality. Adequate bioinformatics support was essential in pharmacogenomics research in view of the enormous amount of whole-genome data involved. These whole-genome findings will ultimately facilitate personalized asthma pharmacotherapy that allows
us to choose among treatment options that will likely be effective to any particular patient. However, more resources and collaborative efforts are required to advance the pharmacogenomics research.