Gene: IL1RL1

9173
DER4|FIT-1|IL33R|ST2|ST2L|ST2V|T1
interleukin 1 receptor like 1
protein-coding
2q12.1
Ensembl:ENSG00000115602 MIM:601203 Vega:OTTHUMG00000130782 UniprotKB:Q01638
NC_000002.12
PubMed
0   ANCO-SNPs
ND
3   
8.840e-1 (AD)  9.863e-1 (ND)   (Frontal_Cortex)
NA (AD)  NA (ND)

DNA Methylation

There is no related methylation information for this gene.

Gene Expression in Different Tissues

Temporal and Spatial Expressions (BrainSpan)

Footnote:
SC: sub-cortical regions; SM: sensory-motor regions; FC: frontal cortex; and TP: temporal-parietal cortex
ST1: fetal (13 - 26 postconception weeks), ST2: early infancy to late childhood (4 months to 11 years), and ST3: adolescence to adulthood (13 - 23 years)
The bar shown representes average value of the expressions.

Top Co-expressed Genes in Brain-Frontal Cortex (BA9) (GTEx v7)

Top 10 positively co-expressed genes

Gene Symbol Pearson Correlation Coefficient
IL18R10.892
SOCS30.704
IL4R0.698
MT1A0.686
YBX30.684
TNFRSF6B0.681
PLIN20.681
CEBPD0.68
CDK20.679
GPR40.678

Top 10 negatively co-expressed genes

Gene Symbol Pearson Correlation Coefficient
RERGL-0.458
WNT7A-0.456
HAPLN1-0.441
KCNMB2-0.438
BEAN1-0.435
CPLX3-0.426
KIT-0.426
CNTN6-0.421
KCNIP3-0.417
NEUROD6-0.417

Drugs/Compounds

    There is no DrugBank record for this gene !

ID Drug Name Action PubMed
C0252231,4-dioxane"1,4-dioxane results in increased expression of IL1RL1 protein"20025956
C5486512-(1'H-indolo-3'-carbonyl)thiazole-4-carboxylic acid methyl ester2-(1'H-indolo-3'-carbonyl)thiazole-4-carboxylic acid methyl ester results in decreased expression of IL1RL1 mRNA19933214
C5112952,2',4,4'-tetrabromodiphenyl ether"2,2',4,4'-tetrabromodiphenyl ether results in increased expression of IL1RL1 mRNA"25614096
C0109142,4-diaminotoluene"2,4-diaminotoluene results in increased expression of IL1RL1 mRNA"20713471
C0230353,4,5,3',4'-pentachlorobiphenyl"3,4,5,3',4'-pentachlorobiphenyl results in increased expression of IL1RL1 mRNA"23196670
C0144643,4-dichloroaniline"3,4-dichloroaniline results in increased expression of IL1RL1 mRNA"24172598
C0275764-hydroxy-2-nonenal4-hydroxy-2-nonenal results in decreased expression of IL1RL1 mRNA19191707
C0312266-O-palmitoylascorbic acid6-O-palmitoylascorbic acid results in increased expression of IL1RL1 protein20025956
D000082AcetaminophenAcetaminophen affects the expression of IL1RL1 mRNA17562736
D000082AcetaminophenAcetaminophen results in increased expression of IL1RL1 mRNA17585979
D020106AcrylamideAcrylamide results in increased expression of IL1RL1 protein20025956
D016604Aflatoxin B1Aflatoxin B1 results in decreased methylation of IL1RL1 gene27153756
D016604Aflatoxin B1Aflatoxin B1 results in increased expression of IL1RL1 mRNA22100608|2715375
D000485AllergensIL1RL1 gene mutant form results in decreased susceptibility to Allergens25015831
D000643Ammonium ChlorideAmmonium Chloride affects the expression of IL1RL1 mRNA16483693
D039741Antigens, Dermatophagoides"Antigens, Dermatophagoides results in increased expression of IL1RL1 mRNA"26304032
D001151ArsenicArsenic affects the expression of IL1RL1 mRNA18315880
D017638Asbestos, Crocidolite"Asbestos, Crocidolite affects the expression of IL1RL1 mRNA"25757056
D017638Asbestos, Crocidolite"Asbestos, Crocidolite results in increased expression of IL1RL1 mRNA"25351596
C006703benzo(b)fluoranthenebenzo(b)fluoranthene results in decreased expression of IL1RL1 mRNA26377693
D019817Benzoic AcidBenzoic Acid results in increased expression of IL1RL1 protein20025956
D001564Benzo(a)pyreneBenzo(a)pyrene results in decreased expression of IL1RL1 mRNA22610609
D001564Benzo(a)pyreneBenzo(a)pyrene results in increased expression of IL1RL1 mRNA20713471
D004958EstradiolEstradiol results in increased expression of IL1RL1 mRNA18692832
D004958Estradiol[Progesterone co-treated with Estradiol] results in increased expression of IL1RL1 mRNA17404688|1869283
D004958EstradiolEstradiol results in increased expression of IL1RL1 mRNA19484750
D004958EstradiolEstradiol results in increased expression of IL1RL1 protein20025956
C006780bisphenol Abisphenol A results in decreased expression of IL1RL1 mRNA25181051
D002083Butylated HydroxyanisoleButylated Hydroxyanisole results in increased expression of IL1RL1 mRNA19000923
D002084Butylated HydroxytolueneButylated Hydroxytoluene results in increased expression of IL1RL1 mRNA19000923
C018475butyraldehydebutyraldehyde results in increased expression of IL1RL1 mRNA26079696
D002104CadmiumCadmium results in increased expression of IL1RL1 mRNA20105457|2112074
D019256Cadmium ChlorideCadmium Chloride results in decreased expression of IL1RL1 mRNA26472689
D019256Cadmium ChlorideCadmium Chloride results in increased methylation of IL1RL1 promoter22457795
D002110CaffeineCaffeine results in increased expression of IL1RL1 protein20025956
D002251Carbon TetrachlorideIL1RL1 protein affects the reaction [Carbon Tetrachloride results in increased expression of IL10 protein]17412915
D002251Carbon TetrachlorideIL1RL1 protein affects the reaction [Carbon Tetrachloride results in increased expression of IL13 protein]17412915
D002251Carbon TetrachlorideIL1RL1 protein affects the reaction [Carbon Tetrachloride results in increased expression of IL4 protein]17412915
D002251Carbon TetrachlorideIL1RL1 protein affects the reaction [Carbon Tetrachloride results in increased expression of IL5 protein]17412915
D002713ChlorineChlorine results in decreased expression of IL1RL1 mRNA18636392
D002713Chlorine[Ozone co-treated with Chlorine] results in decreased expression of IL1RL1 mRNA18636392
D019826Cholic AcidCholic Acid results in increased expression of IL1RL1 protein20025956
D002793Cholic Acids[1-Naphthylisothiocyanate co-treated with Cholic Acids] affects the expression of IL1RL1 mRNA27344345
D002793Cholic Acids[Ethinyl Estradiol co-treated with Cholic Acids] affects the expression of IL1RL1 mRNA27344345
D002793Cholic Acids[Methyltestosterone co-treated with Cholic Acids] affects the expression of IL1RL1 mRNA27344345
C074702chromium hexavalent ionchromium hexavalent ion affects the expression of IL1RL1 mRNA28472532
C018021cobaltous chloridecobaltous chloride results in decreased expression of IL1RL1 mRNA19320972
D003300Copper[NSC 689534 binds to Copper] which results in increased expression of IL1RL1 mRNA20971185
D003345CorticosteroneCorticosterone results in decreased expression of IL1RL1 mRNA15755911
D016572CyclosporineCyclosporine results in increased expression of IL1RL1 mRNA20106945|2214713
D0150842,4-Dichlorophenoxyacetic Acid"2,4-Dichlorophenoxyacetic Acid results in decreased expression of IL1RL1 mRNA"15878651
D013759DronabinolDronabinol results in decreased expression of IL1RL1 mRNA16616335
C007262deoxynivalenoldeoxynivalenol results in increased expression of IL1RL1 mRNA26304032
D003907Dexamethasone[INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin] results in increased expression of IL1RL1 mRNA28628672
D003907Dexamethasone[Dexamethasone co-treated with rosiglitazone co-treated with 1-Methyl-3-isobutylxanthine co-treated with INS1 protein] results in decreased expression of IL1RL1 mRNA16054899
D003907DexamethasoneDexamethasone results in increased expression of IL1RL1 mRNA22733784
D002945Cisplatin[Cisplatin co-treated with jinfukang] results in decreased expression of IL1RL1 mRNA27392435
D002945CisplatinCisplatin results in decreased expression of IL1RL1 mRNA22023808
D004051Diethylhexyl PhthalateDiethylhexyl Phthalate results in increased expression of IL1RL1 mRNA19000923
D000875AnthralinAnthralin results in increased expression of IL1RL1 protein20025956
D002117CalcitriolCalcitriol results in increased expression of IL1RL1 mRNA12040012|1600243
D002117CalcitriolKetoconazole promotes the reaction [Calcitriol results in increased expression of IL1RL1 mRNA]12040012
D0151279,10-Dimethyl-1,2-benzanthracene"9,10-Dimethyl-1,2-benzanthracene results in increased expression of IL1RL1 protein"20025956
D0151279,10-Dimethyl-1,2-benzanthracene"9,10-Dimethyl-1,2-benzanthracene results in decreased expression of IL1RL1 mRNA"19480007
D0198131,2-Dimethylhydrazine"[APC protein affects the susceptibility to 1,2-Dimethylhydrazine] which results in increased expression of IL1RL1 mRNA"27840820
D004137DinitrochlorobenzeneDinitrochlorobenzene results in increased expression of IL1RL1 mRNA20146380
D004137DinitrochlorobenzeneDinitrochlorobenzene results in increased expression of IL1RL1 mRNA11708898
D004221DisulfiramDisulfiram results in decreased expression of IL1RL1 mRNA20530235
D004997Ethinyl Estradiol[Ethinyl Estradiol co-treated with Cholic Acids] affects the expression of IL1RL1 mRNA27344345
C024555ferric chlorideferric chloride results in increased expression of IL1RL1 protein20025956
C029451ferrous chlorideferrous chloride results in increased expression of IL1RL1 protein20025956
D005419FlavonoidsFlavonoids results in increased expression of IL1RL1 mRNA18035473
D005492Folic Acid[Folic Acid affects the susceptibility to Pemetrexed] which affects the expression of IL1RL1 mRNA22975265
D005557FormaldehydeFormaldehyde results in increased expression of IL1RL1 mRNA12679049
C039281furanfuran results in decreased methylation of IL1RL1 gene22079235
C039281furanfuran results in increased expression of IL1RL1 mRNA27387713
C508665gold (III) porphyrin 1agold (III) porphyrin 1a results in increased expression of IL1RL1 mRNA16206274
D006418HemeHeme metabolite results in decreased expression of IL1RL1 mRNA19191707
D017313FenretinideFenretinide results in decreased expression of IL1RL1 mRNA28973697
D007213Indomethacin[INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin] results in increased expression of IL1RL1 mRNA28628672
D015759Ionomycin[Tetradecanoylphorbol Acetate co-treated with Ionomycin] results in decreased expression of IL1RL1 mRNA25613284
D0150561-Methyl-3-isobutylxanthine[INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin] results in increased expression of IL1RL1 mRNA28628672
D0150561-Methyl-3-isobutylxanthine[Dexamethasone co-treated with rosiglitazone co-treated with 1-Methyl-3-isobutylxanthine co-treated with INS1 protein] results in decreased expression of IL1RL1 mRNA16054899
C544151jinfukang[Cisplatin co-treated with jinfukang] results in decreased expression of IL1RL1 mRNA27392435
C544151jinfukangjinfukang results in decreased expression of IL1RL1 mRNA27392435
D007654KetoconazoleKetoconazole promotes the reaction [Calcitriol results in increased expression of IL1RL1 mRNA]12040012
C011890kojic acidkojic acid results in increased expression of IL1RL1 mRNA19000923
C482199lipopolysaccharide, E coli O55-B5"lipopolysaccharide, E coli O55-B5 results in decreased expression of IL1RL1 mRNA"24972896
D008070LipopolysaccharidesIL1RL1 protein inhibits the reaction [Lipopolysaccharides results in increased expression of IL6 mRNA]21352201
D008070LipopolysaccharidesIL1RL1 protein inhibits the reaction [Lipopolysaccharides results in increased expression of TLR4 mRNA]21352201
D008070LipopolysaccharidesIL1RL1 protein inhibits the reaction [Lipopolysaccharides results in increased expression of TNF mRNA]21352201
D058185Magnetite Nanoparticles[Succimer binds to Magnetite Nanoparticles] which results in increased expression of IL1RL1 mRNA21641980
D008345ManganeseManganese results in decreased expression of IL1RL1 mRNA26745496
C025340manganese chloridemanganese chloride results in decreased expression of IL1RL1 mRNA26745496
D008727MethotrexateMethotrexate results in decreased expression of IL1RL1 mRNA17400583
D008727MethotrexateMethotrexate results in increased expression of IL1RL1 mRNA24449571|2465727
D008748MethylcholanthreneMethylcholanthrene results in increased expression of IL1RL1 mRNA20713471
D008777Methyltestosterone[Methyltestosterone co-treated with Cholic Acids] affects the expression of IL1RL1 mRNA27344345
C011309mezereinmezerein results in increased expression of IL1RL1 mRNA19000923
C500085muraglitazarmuraglitazar results in decreased expression of IL1RL1 mRNA21515302
D009151Mustard GasMustard Gas results in increased expression of IL1RL1 mRNA25102026
D009151Mustard GasMustard Gas results in increased expression of IL1RL1 mRNA18955075
D037742Nanotubes, Carbon"Nanotubes, Carbon analog affects the expression of IL1RL1 mRNA"25554681
D037742Nanotubes, Carbon"Nanotubes, Carbon results in decreased expression of IL1RL1 mRNA"25554681
D0150581-Naphthylisothiocyanate[1-Naphthylisothiocyanate co-treated with Cholic Acids] affects the expression of IL1RL1 mRNA27344345
C017096n-butoxyethanoln-butoxyethanol results in increased expression of IL1RL1 mRNA19812364
D009532NickelNickel results in increased expression of IL1RL1 mRNA24768652|2558310
C558013NSC 689534[NSC 689534 binds to Copper] which results in increased expression of IL1RL1 mRNA20971185
D019319Okadaic AcidOkadaic Acid results in increased expression of IL1RL1 mRNA19000923
C030110oxaliplatin[oxaliplatin co-treated with Topotecan] results in increased expression of IL1RL1 mRNA25729387
D010100OxygenOxygen deficiency results in decreased expression of IL1RL1 mRNA26516004
D010126OzoneIL1RL1 protein affects the reaction [[LEP gene mutant form results in increased susceptibility to Ozone] which results in increased expression of CCL4 protein]27472835
D010126OzoneIL1RL1 protein affects the reaction [[LEP gene mutant form results in increased susceptibility to Ozone] which results in increased expression of CXCL1 protein]27472835
D010126OzoneIL1RL1 protein affects the reaction [[LEP gene mutant form results in increased susceptibility to Ozone] which results in increased expression of IL13 protein]27472835
D010126OzoneIL1RL1 protein affects the reaction [[LEP gene mutant form results in increased susceptibility to Ozone] which results in increased expression of IL5 protein]27472835
D010126OzoneIL1RL1 protein affects the reaction [[LEP gene mutant form results in increased susceptibility to Ozone] which results in increased expression of IL6 protein]27472835
D010126Ozone[Ozone co-treated with Chlorine] results in decreased expression of IL1RL1 mRNA18636392
D010126OzoneOzone results in increased expression of IL1RL1 mRNA16716893
C010272palytoxinpalytoxin results in increased expression of IL1RL1 protein20025956
D052638Particulate MatterParticulate Matter results in decreased expression of IL1RL1 mRNA17987463
C008776pelargonic acidpelargonic acid results in increased expression of IL1RL1 mRNA11379042
D000068437Pemetrexed[Folic Acid affects the susceptibility to Pemetrexed] which affects the expression of IL1RL1 mRNA22975265
C046012pentanalpentanal results in increased expression of IL1RL1 mRNA26079696
C101814perfluoro-n-undecanoic acidperfluoro-n-undecanoic acid results in decreased expression of IL1RL1 mRNA23602845
D010615PhenacetinPhenacetin results in increased expression of IL1RL1 mRNA19000923
D010634PhenobarbitalPhenobarbital affects the expression of IL1RL1 mRNA19159669
D010634PhenobarbitalPhenobarbital results in increased expression of IL1RL1 mRNA19000923
C006253pirinixic acid[pirinixic acid binds to and results in increased activity of PPARA protein] which results in decreased expression of IL1RL1 mRNA19710929
D011136PolysorbatesPolysorbates results in increased expression of IL1RL1 protein20025956
D011137PolystyrenesPolystyrenes analog results in increased expression of IL1RL1 mRNA25102311
D011137PolystyrenesPolystyrenes results in increased expression of IL1RL1 mRNA25102311
D011374Progesterone[Progesterone co-treated with Estradiol] results in increased expression of IL1RL1 mRNA17404688|1869283
D011374ProgesteroneProgesterone results in increased expression of IL1RL1 mRNA17404688|1869283
D011374ProgesteroneProgesterone results in increased expression of IL1RL1 mRNA19000923
D011374ProgesteroneProgesterone results in decreased expression of IL1RL1 mRNA20726854
C029658propionic acidpropionic acid results in increased expression of IL1RL1 protein20025956
D011794QuercetinQuercetin results in increased expression of IL1RL1 mRNA21632981
D011794QuercetinQuercetin affects the expression of IL1RL1 mRNA18178720
C089730rosiglitazone[Dexamethasone co-treated with rosiglitazone co-treated with 1-Methyl-3-isobutylxanthine co-treated with INS1 protein] results in decreased expression of IL1RL1 mRNA16054899
C089730rosiglitazonerosiglitazone results in increased expression of IL1RL1 mRNA21515302
D012439SaccharinSaccharin results in increased expression of IL1RL1 mRNA19000923
C078903seocalcitolseocalcitol results in increased expression of IL1RL1 mRNA12040012
D017632Asbestos, Serpentine"Asbestos, Serpentine results in increased expression of IL1RL1 mRNA"24160326
D017632Asbestos, Serpentine"Asbestos, Serpentine results in increased expression of IL1RL1 mRNA"23917077
D012822Silicon DioxideSilicon Dioxide results in increased expression of IL1RL1 mRNA22300531|2535159
D012834SilverSilver results in increased expression of IL1RL1 mRNA27131904
D019821SimvastatinSimvastatin results in decreased expression of IL1RL1 mRNA16414398
D012906SmokeSmoke results in increased expression of IL1RL1 mRNA21095227
C016104sodium bichromatesodium bichromate results in increased expression of IL1RL1 mRNA22155349
C016104sodium bichromatesodium bichromate results in increased expression of IL1RL1 mRNA22561333
D012977Sodium NitriteSodium Nitrite results in increased expression of IL1RL1 protein20025956
C013690styrene oxidestyrene oxide results in increased expression of IL1RL1 protein20025956
D004113Succimer[Succimer binds to Magnetite Nanoparticles] which results in increased expression of IL1RL1 mRNA21641980
D013412SulfadimethoxineSulfadimethoxine results in increased expression of IL1RL1 mRNA19000923
D013749TetrachlorodibenzodioxinTetrachlorodibenzodioxin results in decreased expression of IL1RL1 mRNA19933214
D013755Tetradecanoylphorbol AcetateTetradecanoylphorbol Acetate results in increased expression of IL1RL1 mRNA19000923
D013755Tetradecanoylphorbol Acetate[Tetradecanoylphorbol Acetate co-treated with Ionomycin] results in decreased expression of IL1RL1 mRNA25613284
D013893ThiramThiram results in decreased expression of IL1RL1 mRNA20530235
D014028Tobacco Smoke PollutionTobacco Smoke Pollution results in increased expression of IL1RL1 mRNA27404394|2786577
D014028Tobacco Smoke PollutionTobacco Smoke Pollution affects the expression of IL1RL1 mRNA20133372
D014051Toluene 2,4-Diisocyanate"Toluene 2,4-Diisocyanate results in decreased expression of IL1RL1 mRNA"11379042
D019772Topotecan[oxaliplatin co-treated with Topotecan] results in increased expression of IL1RL1 mRNA25729387
D019772TopotecanTopotecan results in increased expression of IL1RL1 mRNA25729387
D014118Toxins, Biological"Toxins, Biological affects the expression of IL1RL1 mRNA"19682533
D014212TretinoinTretinoin results in decreased expression of IL1RL1 mRNA20530235
D014241TrichloroethyleneTrichloroethylene results in increased methylation of IL1RL1 gene27618143
C015559trimellitic anhydridetrimellitic anhydride results in increased expression of IL1RL1 mRNA11708898
D014302Trinitrobenzenesulfonic AcidTrinitrobenzenesulfonic Acid results in increased expression of IL1RL1 mRNA17982090
C057693troglitazonetroglitazone results in increased expression of IL1RL1 mRNA28973697
C057693troglitazonetroglitazone results in increased expression of IL1RL1 mRNA21515302
D014635Valproic AcidValproic Acid results in decreased expression of IL1RL1 mRNA29154799
D014635Valproic AcidValproic Acid affects the expression of IL1RL1 mRNA17292431|1796380
D014638VanadatesVanadates results in increased expression of IL1RL1 mRNA19000923
D001335Vehicle EmissionsVehicle Emissions results in decreased expression of IL1RL1 mRNA17987463
D001335Vehicle EmissionsVehicle Emissions results in increased methylation of IL1RL1 gene25560391
D001335Vehicle EmissionsVehicle Emissions analog results in increased expression of IL1RL1 mRNA15541757
D001335Vehicle EmissionsVehicle Emissions results in increased expression of IL1RL1 mRNA19465080
C016837zinc chloridezinc chloride results in increased expression of IL1RL1 mRNA19000923

GO/Pathway

GO ID GO Term Qualifier Evidence PubMed
GO:0002113interleukin-33 binding-IEA-  
GO:0002114interleukin-33 receptor activity-IEA-  
GO:0004896cytokine receptor activity-TAS10191101  
GO:0004908interleukin-1 receptor activity-IEA-  
GO:0005515protein binding-IPI8621446  16286016  25416956  
GO ID GO Term Qualifier Evidence PubMed
GO:0002826negative regulation of T-helper 1 type immune response-IEA-  
GO:0006955immune response-NAS10527832  
GO:0007165signal transduction-TAS1482686  
GO:0032689negative regulation of interferon-gamma production-IEA-  
GO:0032754positive regulation of interleukin-5 production-IEA-  
GO:0038172interleukin-33-mediated signaling pathway-TAS-  
GO:0043032positive regulation of macrophage activation-IEA-  
GO:0043124negative regulation of I-kappaB kinase/NF-kappaB signaling-IEA-  
GO:0050729positive regulation of inflammatory response-IEA-  
GO:0090197positive regulation of chemokine secretion-IEA-  
GO ID GO Term Qualifier Evidence PubMed
GO:0005576extracellular region-IEA-  
GO:0005886plasma membrane-TAS-  
GO:0009897external side of plasma membrane-IEA-  
GO:0016021integral component of membrane-IEA-  
KEGG ID KEGG Term
Reactome ID Reactome Term Evidence
R-HSA-1257604PIP3 activates AKT signalingTAS
R-HSA-1280215Cytokine Signaling in Immune systemTAS
R-HSA-162582Signal TransductionTAS
R-HSA-168256Immune SystemTAS
R-HSA-199418Negative regulation of the PI3K/AKT networkTAS
R-HSA-446652Interleukin-1 family signalingTAS
R-HSA-449147Signaling by InterleukinsTAS
R-HSA-6811558PI5P, PP2A and IER3 Regulate PI3K/AKT SignalingTAS
R-HSA-9006925Intracellular signaling by second messengersTAS
R-HSA-9014843Interleukin-33 signalingTAS

Interactions (STRING v10.5, Interaction Score >= 0.400)

Publications (Co-occurrence of gene symbol strings and ANCO-Dependence terms)

PMID Title (Year) Author Journal
23028483Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. (2012)Ramasamy APLoS One
20008879Genome-wide association studies: what do they teach us about asthma and chronic obstructive pulmonary disease? (2009 Dec)Boezen HMProc Am Thorac Soc
27058054Asthma susceptibility variants are more strongly associated with clinically similar subgroups. (2016 Nov)Lavoie-Charland EJ Asthma