{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:02:33Z","timestamp":1790942553106,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2004,10,12]],"date-time":"2004-10-12T00:00:00Z","timestamp":1097539200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background\n\t\t\t\t\t<\/jats:bold> Development of asthma is likely to depend on a complex interaction between environmental and genetic factors. Several groups have suggested the gene of the IL\u20104 receptor \u03b1 chain (IL4R) as a candidate gene for the development of asthma, although association with single polymorphisms has shown contradicting results.<\/jats:p><jats:p><jats:bold>Objective\n\t\t\t\t\t<\/jats:bold> We chose to analyse IL4R gene haplotypes and assess their possible relevance in susceptibility to asthma and to certain clinical phenotypes.<\/jats:p><jats:p><jats:bold>Methods\n\t\t\t\t\t<\/jats:bold> IL4R gene haplotypes were analysed, based on the three markers C\u20103223T, Q551R and I50V, using the expectation\u2013maximization algorithm, in 170 atopic asthma patients and 350 controls, all adult Swedish Caucasians.<\/jats:p><jats:p><jats:bold>Results\n\t\t\t\t\t<\/jats:bold> Our data showed significantly higher levels of soluble IL\u20104R (sIL\u20104R) in asthma patients compared with controls (<jats:italic>P<\/jats:italic>&lt;0.0001). Furthermore, we showed a significant association between the IL4R haplotype containing the alleles T\u20103223, V50 and R551 (TVR) of the IL4R gene, and susceptibility to atopic asthma, with a frequency of 6.5% in the patients compared with 1% in the controls (<jats:italic>P<\/jats:italic>&lt;0.0005). A subgroup of patients with heterozygous or homozygous state for the T\u20103223, V50 and R551 alleles, also had lower levels of sIL\u20104R in their circulation compared with patients with homozygous state in the C\u20103223, I50 and Q551 alleles (<jats:italic>P<\/jats:italic>&lt;0.05) and showed less severe asthma according to lung function test (<jats:italic>P<\/jats:italic>&lt;0.05). Analysis of single markers showed the T\u20103223 IL4R allele to associate with lower serum levels of sIL\u20104 receptor (<jats:italic>P<\/jats:italic>&lt;0.0001) and patients carrying the T allele also had more symptoms of active asthma (wheezing, <jats:italic>P<\/jats:italic>&lt;0.01; coughing, <jats:italic>P<\/jats:italic>&lt;0.05 and breathing difficulties, <jats:italic>P<\/jats:italic>&lt;0.01).<\/jats:p><jats:p><jats:bold>Conclusion\n\t\t\t\t\t<\/jats:bold> Our data suggest that asthmatic patients with low levels of sIL\u20104 receptor may represent a genetically distinct subgroup of atopic asthma. TVR haplotype analyses confirm the importance of IL4R as a candidate gene for susceptibility to asthma. This finding may have implications for the understanding of the pathogenesis of asthma and possibly for the development of more specific therapies.<\/jats:p>","DOI":"10.1111\/j.1365-2222.2004.02069.x","type":"journal-article","created":{"date-parts":[[2004,10,12]],"date-time":"2004-10-12T09:10:51Z","timestamp":1097572251000},"page":"1570-1575","source":"Crossref","is-referenced-by-count":49,"title":["Haplotypes of the interleukin\u20104 receptor \u03b1 chain gene associate with susceptibility to and severity of atopic asthma"],"prefix":"10.1111","volume":"34","author":[{"given":"A.\u2010M.","family":"Hyt\u00f6nen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"L\u00f6whagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Arvidsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Balder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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