Genetic polymorphisms and associated susceptibility to asthma

Figures & data

Table 1 Well-replicated loci identified through candidate-gene studies

Gene	Chromosomal locus	Function
IL10	1q31-q32	Cytokine – immune regulation
CTLA4	2q33	Control/inhibition of T cell responses/immune regulation
IL13	5q31	Induces TH2 effector functions
IL4	5q31.1	TH2 differentiation
CD14	5q31.1	Microbe detection – recognizes pathogen associated molecular patterns
HAVCR1	5q33.2	T cell responses – hepatitis A virus receptor
LTC4S	5q35	Leukotriene synthase – inflammatory mediator
LTA	6p21.3	Inflammatory mediator
TNF	6p21.3	Inflammatory mediator
HLA-DRB1	6p21	Major histocompatibility complex class II – antigen presentation
HLA-DQB1	6p21
HLA-DPB1	6p21
FCER1B	11q13	Receptor for IgE – atopy
IL18	11q22.2-q22.3	Inflammation
STAT6	12q13	IL-4 and IL-13 signaling
CMA1	14q11.2	Chymase – mast cell expressed serine protease
IL4R	16p12.1-p12.2	Alpha chain of receptors for IL-4 and IL-13
FLG	1q21.3	Epithelial integrity and barrier function
SPINK5	5q32	Epithelial serine protease inhibitor
CC16	11q12.3-q13.1	Potential immunoregulatory function – epithelial expression
NOS1	12q24.2-q24.31	Nitric oxide synthase – cellular communication
CCL11	17q21.1-q21.2	Eoxtaxin-1 – eosinophil chemoattractant
CCL5	17q11.2-q12	RANTES – chemoattractant for T cells, eosinophils, basophils
GSTM1	1p13.3	Detoxification, removal of products of oxidative stress
ADRB2	5q31-q32	Smooth muscle relaxation
GPRA	7p14.3	Regulation of metalloprotease expression, neuronal effects
NAT2	8p22	Detoxification
GSTP1	11q13	Detoxification, removal of products of oxidative stress
ACE	17q23.3	Regulation of inflammation
TBXA2R	19p13.3	Platelet aggregation
TGFB1	19q13.1	Influences cell growth, differentiation, proliferation, apoptosis
ADAM33	20p13	Cell–cell and cell–matrix interactions
GSTT1	22q11.23	Detoxification, removal of products of oxidative stress

Abbreviations: IgE, immunoglobulin E; IL, interleukin; RANTES, regulated and normal T cell expressed and secreted; T_H, Thelper.

Table 2 Loci identified though linkage studies and positional cloning

Gene	Chromosomal locus	Reference
DPP10	2q14.1	Allen et al^Citation68
GPRA	7p14.3	Laitinen et al^Citation39
HLAG	6p21.33	Nicolae et al^Citation69
ADAM33	20p13	Van Eerdewegh et al^Citation37
PHF11	13q14.3	Zhang et al^Citation70
CYFIP2	5q33.3	Noguchi et al^Citation67
IRAK3	12q14	Balaci et al^Citation130
COL6A5	3q21	Söderhäll et al^Citation38
OPN3/CHML	1qter	White et al^Citation131

Table 3 Genome-wide association study loci referenced in this review

Reported gene	Locus	Top single nucleotide polymorphism	Endpoint analyzed	Reference
ORMDL3	17q12	rs7216389	Asthma	Moffatt et al^Citation71
CHI3L1	1q32.1	rs4950928	Asthma/YKL-40 serum levels	Ober et al^Citation88
IL1RL1	2q12.1	rs1420101	Asthma/blood	Gudbjartsson et al^Citation91
IKZF2	5q31.1	rs12619285	Eosinophil count
GATA2	3q21.3	rs4857855
IL5	2q12.1	rs4143832
SH2B3	12q24.12	rs3184504
TLE4	9q21.31	rs2378383	Asthma	Hancock et al^Citation80
PDE4D	5q12.1	rs1588265	Asthma	Himes et al^Citation42
PDE11A	2q31.2	rs11684634	Asthma	DeWan et al^Citation79
RAD50	5q31.1	rs2244012	Asthma	Li et al^Citation21
HLA-DR/DQ	6p21.32	rs3998159
ADRA1B	5q33	rs10515807	Asthma	Mathias et al^Citation132
PRNP	20p12	rs6052761
DPP10	12q12.3	rs1435879
IL1RL1/IL18R1	2q12.1	rs3771166	Asthma	Moffatt et al^Citation26
HLA-DQ	6p21.32	rs9273349	Childhood-onset asthma
IL33	9p24.1	rs1342326
SMAD3	15q22.33	rs744910
IL2RB	22q12.3	rs2284033
ORMDL3/GSDMB	17q12	rs2305480
HLA-DPA1/HLA-DPB1	6p21.3	rs987870	Pediatric asthma	Noguchi et al^Citation133
DENND1B	1q31.3	rs2786098	Pediatric asthma	Sleiman et al^Citation82
IL6R	1q21.3	rs4129267	Asthma	Ferreira et al^Citation86
C11orf30/LRRC32	11q13.5	rs7130588
USP38-GAB1	4q31	rs7686660	Asthma	Hirota et al^Citation85
TSLP/WDR36	5q22	rs1837253
NOTCH4/HLA-DRA/	6p21.32	rs404860
HLA-DQA2/IKZF4	6p21.32	rs404860
LOC338591	10p14	rs10508372
IKZF4/CDK2	12q13	rs1701704
GSDMB	17q12	rs11078927	Asthma in four ethnically diverse North American populations	Torgerson et al^Citation87
IL1RL1	2q12.1	rs10173081
TSLP	5q22.1	rs1837253
IL33	9p24.1	rs2381416
PYHIN1	1q23.1	rs1102000
C11orf71	11q23.2	rs11214966
CRCT1	1q21.3	rs4845783
ORMDL3	17q12	rs6503525	Asthma	Ferreira et al^Citation77
C11orf30/LRRC32	11q13.5	rs2155219	Allergic rhinitis/grass sensitization	Ramasamy et al^Citation90
TMEM232/SLCA25A46	5q22.1	rs17513503
HLA region	6p21	rs7775228
FCER1A	1q23.2	rs2251746	IgE levels	Granada et al^Citation134
IL13	5q31.1	rs20541
HLA-A	6p22.1	rs2571391
STAT6/NAB2	12q13.3	rs1059513
DARC	1q23.2	rs13962
HLA-DQA2	6p21.32	rs2858331
FCER1A	1q23.2	rs2427837	Serum IgE levels	Weidinger et al^Citation89
STAT6	12q13	rs12368672
RAD50	5q31.1	rs2706347
CHRNA3/5	15q24	rs8034191	COPD	Pillai et al^Citation135
FAM13A	4q22.1	rs7671167	COPD	Cho et al^Citation136
RAB4B/EGLN2/MIA/CYP2A6	19q13	rs7937	COPD	Cho et al^Citation137
HHIP	4q31.22	rs13147758	FEV1/FVC	Wilk et al^Citation92
HHIP	4q31.22	rs1980057	FEV1/FVC	Hancock et al^Citation93
GPR126	6q24.1	rs3817928	FEV1/FVC
ADAM19	5q33	rs2277027	FEV1/FVC
AGER-PPT2	6p21.3	rs2070600	FEV1/FVC
FAM13A	4q22.1	rs2869967	FEV1/FVC
PTCH1	9q22.32	rs16909898	FEV1/FVC
PID1	2q36.3	rs1435867	FEV1/FVC
HTR4	5q33.1	rs11168048	FEV1/FVC
INTS12-GSTCD-NPNT	4q24	rs17331332	FEV1
TNS1	2q35	rs2571445	FEV1	Repapi et al^Citation94
GSTCD	4q24	rs10516526	FEV1
HHIP	4q31.22	rs12504628	FEV1/FVC
HTR4	5q33.1	rs3995090	FEV1
AGER	6p21.32	rs2070600	FEV1/FVC
THSD4	15q23	rs12899618	FEV1/FVC
MFAP2	1p36.13	rs2284746	FEV1/FVC	Soler Artigas et al^Citation138
TGFB2	1q41	rs993925	FEV1/FVC
HDAC4	2q37.3	rs12477314	FEV1/FVC
RARB	3p24	rs1529672	FEV1/FVC
MECOM	3q26	rs1344555	FEV1
SPATA9	5q15	rs153916	FEV1/FVC
ZKSCAN3	6p22.1	rs6903828	FEV1
NCR3	6p21.3	rs2857595	FEV1/FVC
ARMC2	6q21	rs2798641	FEV1/FVC
C10orf11	10q22.2	rs11001819	FEV1
LRP1	12q13.3	rs11172113	FEV1/FVC
CCDC38	12q23.1	rs1036429	FEV1/FVC
MMP15	16q21	rs12447804	FEV1/FVC
CFDP1	16q23.1	rs2865531	FEV1/FVC
KCNE2	21q22.1	rs9978142	FEV1/FVC
DLEU7	13q14.3	rs9316500	FEV1	Imboden et al^Citation139

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; IgE, immunoglobulin E.

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