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Association of angiotensin I-converting enzyme gene polymorphisms with aspirin intolerance in asthmatics

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dc.contributor.authorKim, T-H-
dc.contributor.authorChang, H-S-
dc.contributor.authorPark, S-M-
dc.contributor.authorNam, B-Y-
dc.contributor.authorPark, J-S-
dc.contributor.authorRhim, T-
dc.contributor.authorPark, H-S-
dc.contributor.authorKim, M-K-
dc.contributor.authorChoi, I S-
dc.contributor.authorCho, S H-
dc.contributor.authorChung, I Y-
dc.contributor.authorPark, B-L-
dc.contributor.authorPark, C-S-
dc.contributor.authorShin, H-D-
dc.date.accessioned2010-01-28-
dc.date.available2010-01-28-
dc.date.issued2008-08-30-
dc.identifier.citationClin Exp Allergy. 2008 Nov;38(11):1727-37. Epub 2008 Aug 24.en
dc.identifier.issn1365-2222 (Electronic)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18727619-
dc.identifier.urihttps://hdl.handle.net/10371/45950-
dc.description.abstractBACKGROUND: Aspirin-intolerant asthma (AIA) refers to the development of bronchoconstriction in asthmatic individuals following the ingestion of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). Angiotensin I-converting enzyme (ACE), a membrane-bound peptidase present in the lung, plays a pivotal role in the metabolism of the endogenous peptides involved in the pathogenesis of asthma. METHODS: We screened a Korean asthma cohort (581 asthmatics including 81 aspirin-intolerant asthmatics and 231 aspirin-tolerant asthmatics, and 181 normal controls) for four single nucleotide polymorphisms (SNPs; -262 A>T and -115 T>C in the 5'-flanking region and +5467 T>C [Pro450Pro] and+11860 A>G [Thr776Thr] in the coding region) and one ins/del (+21288 CT) in the ACE gene. RESULTS: None of the SNPs or haplotypes showed any association with the development of asthma, but they were significantly associated with the risk of AIA. Logistic regression indicated that the frequency of the rare alleles of -262 A>T and -115 T>C was higher in subjects with AIA than in subjects with aspirin-tolerant asthma (ATA) (P=0.003-0.01, P( corr)=0.015-0.05). Subjects homozygous for the rare alleles of -262 A>T and -115 T>C showed a greater decline in forced expiratory volume in 1 s (FEV(1)) after aspirin provocation than those homozygous for the common alleles (P<0.05). A luciferase reporter assay indicated that ACE promoters containing the rare -262 A>T allele possessed lower activity than did those containing the common allele (P=0.009). In addition, ACE promoters bearing the rare -115 T>C allele had no luciferase activity. DNA-protein binding assays revealed a band containing the ACE promoter region (including -262 A) and a protein complex. CONCLUSION: The -262 A>T polymorphism in the promoter of the ACE gene is associated with AIA, and the rare allele of -262 A>T may confer aspirin hypersensitivity via the down-regulation of ACE expression.en
dc.language.isoenen
dc.publisherWiley-Blackwellen
dc.subjectAdolescenten
dc.subjectAdulten
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectAspirin/administration & dosage/*adverse effectsen
dc.subjectAsthma/complications/*genetics/*physiopathologyen
dc.subjectBinding Sites/geneticsen
dc.subjectChilden
dc.subjectDrug Hypersensitivity/complications/*genetics/physiopathologyen
dc.subjectFemaleen
dc.subjectForced Expiratory Volume/physiologyen
dc.subjectGene Expression/geneticsen
dc.subjectGene Frequency/geneticsen
dc.subjectHaplotypes/geneticsen
dc.subjectHumansen
dc.subjectLogistic Modelsen
dc.subjectMaleen
dc.subjectMiddle Ageden
dc.subjectPeptidyl-Dipeptidase A/*geneticsen
dc.subjectPolymorphism, Genetic/geneticsen
dc.subjectPolymorphism, Single Nucleotide/genetics/immunologyen
dc.subjectPromoter Regions, Genetic/geneticsen
dc.subjectTranscription Factors/metabolismen
dc.subjectYoung Adulten
dc.titleAssociation of angiotensin I-converting enzyme gene polymorphisms with aspirin intolerance in asthmaticsen
dc.typeArticleen
dc.identifier.doi10.1111/j.1365-2222.2008.03082.x-
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