{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T06:22:37Z","timestamp":1775283757360,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2008,8,24]],"date-time":"2008-08-24T00:00:00Z","timestamp":1219536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background<\/jats:bold>Aspirin\u2010intolerant asthma (AIA) refers to the development of bronchoconstriction in asthmatic individuals following the ingestion of aspirin or other non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs). Angiotensin I\u2010converting enzyme (ACE), a membrane\u2010bound peptidase present in the lung, plays a pivotal role in the metabolism of the endogenous peptides involved in the pathogenesis of asthma.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>We screened a Korean asthma cohort (581 asthmatics including 81 aspirin\u2010intolerant asthmatics and 231 aspirin\u2010tolerant asthmatics, and 181 normal controls) for four single nucleotide polymorphisms (SNPs; \u2212262 A&gt;T and \u2212115 T&gt;C in the 5\u2032\u2010flanking region and +5467 T&gt;C [Pro450Pro] and+11860 A&gt;G [Thr776Thr] in the coding region) and one ins\/del (+21288 CT) in the<jats:italic>ACE<\/jats:italic>gene.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>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 \u2212262 A&gt;T and \u2212115 T&gt;C was higher in subjects with AIA than in subjects with aspirin\u2010tolerant asthma (ATA) (<jats:italic>P<\/jats:italic>=0.003\u20130.01,<jats:italic>P<\/jats:italic><jats:sup>\u2003corr<\/jats:sup>=0.015\u20130.05). Subjects homozygous for the rare alleles of \u2212262 A&gt;T and \u2212115 T&gt;C showed a greater decline in forced expiratory volume in 1\u2003s (FEV<jats:sub>1<\/jats:sub>) after aspirin provocation than those homozygous for the common alleles (<jats:italic>P<\/jats:italic>&lt;0.05). A luciferase reporter assay indicated that<jats:italic>ACE<\/jats:italic>promoters containing the rare \u2212262 A&gt;T allele possessed lower activity than did those containing the common allele (<jats:italic>P<\/jats:italic>=0.009). In addition,<jats:italic>ACE<\/jats:italic>promoters bearing the rare \u2212115 T&gt;C allele had no luciferase activity. DNA\u2013protein binding assays revealed a band containing the<jats:italic>ACE<\/jats:italic>promoter region (including \u2212262 A) and a protein complex.<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>The \u2212262 A&gt;T polymorphism in the promoter of the<jats:italic>ACE<\/jats:italic>gene is associated with AIA, and the rare allele of \u2212262 A&gt;T may confer aspirin hypersensitivity via the down\u2010regulation of<jats:italic>ACE<\/jats:italic>expression.<\/jats:p>","DOI":"10.1111\/j.1365-2222.2008.03082.x","type":"journal-article","created":{"date-parts":[[2008,8,25]],"date-time":"2008-08-25T04:12:29Z","timestamp":1219637549000},"page":"1727-1737","source":"Crossref","is-referenced-by-count":50,"title":["Association of angiotensin I\u2010converting enzyme gene polymorphisms with aspirin intolerance in asthmatics"],"prefix":"10.1111","volume":"38","author":[{"given":"T\u2010H.","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u2010S.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u2010M.","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u2010Y.","family":"Nam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u2010S.","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Rhim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u2010S.","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u2010K.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. 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NIH publication no. 95\u20103659."},{"key":"e_1_2_6_29_2","first-page":"2025","volume-title":"Asthma","author":"Stevenson DD.","year":"1997"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2005.02261.x"},{"key":"e_1_2_6_31_2","first-page":"337","article-title":"Leukotriene\u2010related gene polymorphisms in ASA\u2010intolerant asthma","volume":"114","author":"Choi JH","year":"2004","journal-title":"an association with a haplotype of 5-lipoxygenase"},{"key":"e_1_2_6_32_2","first-page":"1268","article-title":"Identification of new polymorphisms of the angiotensin I\u2010converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two\u2010QTL segregation\u2010linkage analysis","volume":"58","author":"Villard E","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac0258094"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.15.6419"},{"key":"e_1_2_6_35_2","first-page":"331","article-title":"Gametic disequilibrium measures","volume":"117","author":"Hedrick PW.","year":"1987","journal-title":"proceed with caution"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1398-9995.2000.00724.x"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.3109\/02770909909056316"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0954-6111(98)90134-2"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.1.9808032"},{"key":"e_1_2_6_40_2","first-page":"243","article-title":"High frequency of DD polymorphism of the angiotensin\u2010converting enzyme gene in Turkish asthmatic patients","volume":"25","author":"Urhan M","year":"2004","journal-title":"Allergy Asthma Proc"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3038.2006.00452.x"},{"key":"e_1_2_6_42_2","first-page":"331","article-title":"Adducin polymorphism","volume":"45","author":"Bianchi G","year":"2005","journal-title":"detection and impact on hypertension and related disorders"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)92948-F"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706067"},{"key":"e_1_2_6_45_2","first-page":"211","article-title":"Endothelium\u2010dependent contraction induced by substance P incanine cerebral arteries","volume":"64","author":"Shirahase H","year":"1995","journal-title":"involvement of NK1 receptors and thromboxane A2"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.03.003"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2222.2008.03082.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2222.2008.03082.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T17:20:41Z","timestamp":1738344041000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2222.2008.03082.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,22]]},"references-count":45,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2008,11]]}},"alternative-id":["10.1111\/j.1365-2222.2008.03082.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2222.2008.03082.x","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,22]]}}}