Pharmacogenetics of Pediatric Asthma: Current Perspectives

Pharmgenomics Pers Med. 2020 Mar 18:13:89-103. doi: 10.2147/PGPM.S201276. eCollection 2020.

Abstract

Asthma is a chronic respiratory disease that affects 339 million people worldwide and has a considerable impact on the pediatric population. Asthma symptoms can be controlled by pharmacological treatment. However, some patients do not respond to therapy and continue suffering from symptoms, which impair the quality of life of patients and limit their daily activity. Genetic variation has been shown to have a role in treatment response. The aim of this review is to update the main findings described in pharmacogenetic studies of pediatric asthma published from January 1, 2018 to December 31, 2019. During this period, the response to short-acting beta-agonists and inhaled corticosteroids in childhood asthma has been evaluated by eleven candidate-gene studies, one meta-analysis of a candidate gene, and six pharmacogenomic studies. The findings have allowed validating the association of genes previously related to asthma treatment response (ADRB2, GSDMB, FCER2, VEGFA, SPAT2SL, ASB3, and COL2A1), and identifying novel associations (PRKG1, DNAH5, IL1RL1, CRISPLD2, MMP9, APOBEC3B-APOBEC3C, EDDM3B, and BBS9). However, some results are not consistent across studies, highlighting the need to conduct larger studies in diverse populations with more homogeneous definitions of treatment response. Once stronger evidence was established, genetic variants will have the potential to be applied in clinical practice as biomarkers of treatment response enhancing asthma management and improving the quality of life of asthma patients.

Keywords: candidate-gene studies; genome-wide association studies; inhaled corticosteroids; short-acting beta-agonists; treatment response; whole-genome sequencing.

Publication types

  • Review

Grants and funding

Supported by grant SAF2017-83417R by the Spanish Ministry of Economy, Industry, and Competitiveness, the State Research Agency, and the European Regional Development Funds from the European Union (MINECO/AEI/FEDER, UE) to MP-Y and FL-D. AE-O received salary support from grant SAF2017-83417R by the Spanish Ministry of Economy, Industry, and Competitiveness. MP-Y was also supported by the Ramón y Cajal Program by the Spanish Ministry of Economy, Industry, and Competitiveness (RYC-2015-17205).