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Genetic influences on response to asthma pharmacotherapy
1Center for Pediatric Clinical Pharmacology, Pharmacogenetics Center, Nemours Children's Clinic, 807 Children's Way, Jacksonville, FL 32207, USA. jlima@nemours.org.
Abstract:
Asthma is a complex inflammatory disease that affects 300 million people worldwide. Safe and effective drugs control the symptoms but heterogeneity in response is large and attributable, in part, to genetic variation. Polymorphisms in several genes influence response to asthma drugs. The genotype of the ADRB2 Gly16Arg single nucleotide polymorphism (SNP) associates with asthma worsening during continuous therapy with β-agonists. SNPs in four genes influence response to inhaled corticosteroids: CRHR1, ACP, TBX21 and FCER2. Polymorphisms in leukotriene pathway and transporter genes influence response to zileuton and the leukotriene receptor antagonists, including ALOX5, LTA4H, LTC4S, ABCC1 and SLCO2B1. Known sequence variants explain a small fraction of response heterogeneity to asthma drugs. More studies are required to formulate a genetic signature that will lead to the personalization of asthma treatment.
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