Systems biology approaches in asthma pharmacogenomics study

Heung-Woo Park

doi:10.4168/aard.2014.2.5.326

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Park: Systems biology approaches in asthma pharmacogenomics study

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Allergy, Asthma & Respiratory Disease 2014; 2(5): 326-331.

Published online: 28 November 2014

DOI: https://doi.org/10.4168/aard.2014.2.5.326

Systems biology approaches in asthma pharmacogenomics study

Heung-Woo Park

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Correspondence to: Heung-Woo Park. Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. Tel: +82-2-2072-0699, Fax: +82-2-742-3291, guinea71@snu.ac.kr

Received 21 August 2014 Revised 14 September 2014 Accepted 16 September 2014

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).

Abstract

The response to drug treatment in asthma is a complex trait and is markedly variable even in patients with apparently similar clinical features. Pharmacogenomics is a study of variations of human genome characteristics as related to drug response. A traditional candidate-gene approach and genome-wide association studies have provided an increasing list of genes and variants that was associated with asthma medications. However, as phenotypic variations arises from a network of complex interactions among genetic and environmental factors, rather than individual genes, a multidisciplinary, system-level approach is required in order to understand the interrelationships among these factors. Systems biology that studies organisms as integrated and interacting networks of genes, proteins and biochemical reactions can contribute to this. It is likely that the combination of network modeling, functional validation, and integrative-Omics will be needed to move asthma pharmacogenomics closer to clinical relevance.

Keywords: Asthma, Pharmacogenetics, Systems biology

Figures and Tables

Fig. 1

General purpose of a pharmacogenomics study. IL, interleukin.

Fig. 2

Components of system. Node, basic component (e.g. each gene, protein, or metabolite); line, relation between nodes; hub, important node.

Fig. 3

Application of systems biology in pharmacogenomics. (A) outline, (B) Example. g, genetic variant; t, transcript; p, protein; m, metabolite.

Table 1

Typical examples of pharmacogenomics study in asthma using candidate gene approach or GWAS

CAMP, childhood asthma management program; ACRN, asthma clinical research network; CARE, childhood asthma reserch and education; ICS, inhaled corticosteroid; GWAS, genome wide association study.

^*Dahlin A, Litonjua A, Irvin CG, Peters SP, Lima JJ, et al., submitted manuscript.

Table 2

Recent examples of pharmacogenomics study in asthma using systems biology

SNP, single nucleotide polymorphism; BDR, bronchodilator response; eQTL, expression quantitative trait loci; ICS, inhaled corticosteroid; CAMP, childhood asthma management program.

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