{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T05:46:12Z","timestamp":1781243172450,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2006,11,2]],"date-time":"2006-11-02T00:00:00Z","timestamp":1162425600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background\n\t\t\t\t\t<\/jats:bold> Several polymorphisms in the IL\u20104 receptor \u03b1 (<jats:italic>IL4RA<\/jats:italic>) gene have been associated with asthma and atopy, but with variable success in different populations. Immunologic studies suggest that IL4RA may interact with other cytokines and receptors, and gene\u2013gene interactions have also been observed with respect to asthma. Such interactions have been proposed to explain partly the difficulties in replicating association studies.<\/jats:p><jats:p><jats:bold>Methods\n\t\t\t\t\t<\/jats:bold> Using the prospective birth cohort BAMSE, we examined eight single nucleotide polymorphisms (SNPs) and corresponding haplotypes in the <jats:italic>IL4RA<\/jats:italic> gene in relation to wheezing and sensitization up to age 4. We also evaluated potential interaction effects (departure from a multiplicative interaction model) between the <jats:italic>IL4RA<\/jats:italic> SNPs and four SNPs in the IL\u20109 receptor (<jats:italic>IL9R<\/jats:italic>) gene previously associated with childhood wheezing.<\/jats:p><jats:p><jats:bold>Results\n\t\t\t\t\t<\/jats:bold> We found no main effect of the <jats:italic>IL4RA<\/jats:italic> SNPs alone and only weak associations to wheezing and sensitization when haplotypes were considered. Gene\u2013gene interactions between several <jats:italic>IL4RA<\/jats:italic> and <jats:italic>IL9R<\/jats:italic> SNPs with regard to wheezing were observed (<jats:italic>P<\/jats:italic>=0.009), especially between <jats:italic>IL4RA<\/jats:italic> Q576R (rs1801275) and <jats:italic>IL9R<\/jats:italic> rs731476 (<jats:italic>P<\/jats:italic>=0.005). An interaction was also seen between <jats:italic>IL4RA<\/jats:italic> and <jats:italic>IL9R<\/jats:italic> haplotypes.<\/jats:p><jats:p><jats:bold>Conclusion\n\t\t\t\t\t<\/jats:bold> Variants in the <jats:italic>IL4RA<\/jats:italic> gene alone may not exert any major influence on susceptibility to asthma\u2010related diseases in childhood, but in combination with other genes, such as <jats:italic>IL9R<\/jats:italic>, <jats:italic>IL4RA<\/jats:italic> may be an important gene for disease susceptibility.<\/jats:p>","DOI":"10.1111\/j.1365-2222.2006.02577.x","type":"journal-article","created":{"date-parts":[[2006,11,2]],"date-time":"2006-11-02T20:14:38Z","timestamp":1162498478000},"page":"1391-1398","source":"Crossref","is-referenced-by-count":16,"title":["Interaction between variants in the interleukin\u20104 receptor \u03b1 and interleukin\u20109 receptor genes in childhood wheezing: evidence from a birth cohort study"],"prefix":"10.1111","volume":"36","author":[{"given":"E.","family":"Mel\u00e9n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Umerkajeff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Nyberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Zucchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lindstedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Gullst\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Wickman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Pershagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Kere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11,2]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"1","article-title":"Asthma genetics 2006","author":"Ober C","year":"2006","journal-title":"the long and winding road to gene discovery"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1999.00705.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/429418"},{"key":"e_1_2_6_5_2","first-page":"456","article-title":"Upregulation of interleukin\u20104 receptor by interferon\u2010gamma","volume":"31","author":"Yamamoto S","year":"2004","journal-title":"enhanced interleukin-4-induced eotaxin-3 production in airway epithelium"},{"key":"e_1_2_6_6_2","first-page":"230","article-title":"Gene\u2013gene interaction in asthma","volume":"70","author":"Howard TD","year":"2002","journal-title":"IL4RA and IL13 in a Dutch population with asthma"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2004.02015.x"},{"key":"e_1_2_6_8_2","first-page":"489","article-title":"Associations between specific serum IgE response and 6 variants within the genes IL4, IL13, and IL4RA in German children","volume":"113","author":"Liu X","year":"2004","journal-title":"the German Multicenter Atopy Study"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.10.024"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/380908"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.12.582"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1537"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1159\/000073735"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2004.01.006"},{"key":"e_1_2_6_15_2","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.4049\/jimmunol.154.6.2624","article-title":"A cascade of cytokines is responsible for IL\u20109 expression in human T cells. 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