Potential therapeutic targets from genetic and epigenetic approaches for asthma

Table 1 The potential genetic therapeutic targets in airway epithelium for asthma

Genes	Chromosome location	Phenotypes	Identifying methods	Possible pathways related to asthma	Ref.
DPP10	2	Asthma	GWAS/PC	Unknown; Kv4 ion channel complex	[8,20]
TSLP	5	Asthma	GWAS	Airway remodelling; promoting TH2 inflammation	[23,30]
CDHR3	7	Asthma	GWAS	Epithelial polarity; cells interaction and differentiation	[26]
SEMA3D	7	Asthma	GWAS	Airway remodelling; angiogenesis	[27]
SMAD3	15	Asthma	GWAS	Transcriptional modulator; TGFβ pathway	[15]
ORMDL3	17	Asthma	GWAS	Sphingolipid metabolism, ER stress response	[14,15,21,23,25,26]
GSDMB	17	Asthma	GWAS	Epithelium cell growth	[14,15,21,23,25,26]
GSDMA	17	Asthma	GWAS	Cell proliferation	[14,15,21,23,25,26]

PC: Positional cloning; GWAS: Genome-wide association study; TGFβ: Transforming growth factor-beta; ER: Endoplasmic reticulum.

Table 2 The genetic and epigenetic loci modify cytokines and receptors of asthma

Genes	Chromosome location	Phenotypes methods	Identifying and functions in asthma	Possible pathways	Ref.
IL-18R1	2	Asthma	GWAS	Activation of NF-κB, inducing TH-associated cytokines	[15,25]
IL-1RL1	2	Asthma, Eos	GWAS	Receptor for IL-33	[15,23,94]
IL-5RA	3	IgE	Epigenetics	TH2 inflammation, regulating eosinophils	[39]
IL-12A	3	Lung function	GWAS	TH1 regulation, activating IFN-γ	[24]
IL-4	5	IgE	Epigenetics	TH2 inflammation, promoting IgE class switching	[39]
IL-13	5	Asthma, IgE	GWAS/epigenetics	TH2 inflammation, promoting IgE class switching	[15,22]
IL-5	5	Asthma	GWAS/epigenetics	TH2 inflammation, regulating eosinophils	[29,36,94]
IL-9	5	Asthma	Expression profiling	Stimulates cell proliferation and prevents apoptosis	[29]
IL-33	9	Asthma	GWAS	Inducing TH-associated cytokines	[15,23,26,94]
IL-2RA	10	Asthma	Epigenetics	PI3K-Akt signalling pathway and Akt signalling	[38]
IL-4R	16	Asthma	Expression profiling	TH2 inflammation	[28]
IL-12RB1	19	Lung function	GWAS	TH1 regulation, activating IFN-γ	[24]
IL-2RB	22	Asthma	GWAS	Endocytosis and transducer mitogenic signals	[15]

GWAS: Genome-wide association study; IL: Interleukin; IgE: Immunoglobulin E; IFN-γ: Interferon-γ; NF-κB: Nuclear factor kappa-B.

Table 3 The microRNAs and their potential roles in asthma

miRNA	Possible function roles in asthma	Ref.
miR-1	Targeting Mpl to regulate TH2 inflammation and P-selectin in lung endothelium	[109]
miR-126a	Regulating TH2 inflammation, airway hyper-responsiveness, eosinophil recruitment	[110]
miR-221	Mediator IL-6 proliferation in airway smooth muscle	[42]
miR-146a	NF-κB dependent gene, control toll-like receptors and cytokine signalling	[111]
miR-146b	NF-κB dependent gene, control toll-like receptors and cytokine signalling	[111]
miR-150	Down-regulated transcription factor c-Myb to control lymphocyte development	[112]
miR-155	Targeting c-Maf to promote TH2 cells to generate IL-4, IL-5 and IL-10	[115,116]

IL: Interleukin; NF-κB: Nuclear factor kappa-B.