{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T13:18:43Z","timestamp":1771679923341,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,10,6]],"date-time":"2011-10-06T00:00:00Z","timestamp":1317859200000},"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":[[2012,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Distinct receptors likely exist for leukotriene (<jats:styled-content style=\"fixed-case\">LT<\/jats:styled-content>)E<jats:sub>4<\/jats:sub>, a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for <jats:styled-content style=\"fixed-case\">LTE<\/jats:styled-content><jats:sub>4<\/jats:sub>\u2010induced airways inflammation, and P2Y12 antagonism attenuates house dust mite\u2010induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To test for association between variants in the P2Y12 gene (<jats:italic>P2RY12<\/jats:italic>) and lung function in human subjects with asthma, and to examine for gene\u2010by\u2010environment interaction with house dust mite exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Nineteen single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s) in <jats:italic>P2RY12<\/jats:italic> were genotyped in 422 children with asthma and their parents (<jats:italic>n<\/jats:italic>\u00a0=\u00a01266). Using family based methods, we tested for associations between these <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s and five lung function measures. We performed haplotype association analyses and tested for gene\u2010by\u2010environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s in <jats:italic>P2RY12<\/jats:italic> were associated with multiple lung function measures (<jats:italic>P<\/jats:italic>\u2010values 0.006\u20130.025). Haplotypes in <jats:italic>P2RY12<\/jats:italic> were also associated with lung function (<jats:italic>P<\/jats:italic>\u2010values 0.0055\u20130.046). House dust mite exposure modulated associations between <jats:italic>P2RY12<\/jats:italic> and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction <jats:italic>P<\/jats:italic>\u2010values 0.0028\u20130.040).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>The <jats:italic>P2RY12<\/jats:italic> variants were associated with lung function in a large family\u2010based asthma cohort. House dust mite exposure caused significant gene\u2010by\u2010environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2222.2011.03874.x","type":"journal-article","created":{"date-parts":[[2011,10,6]],"date-time":"2011-10-06T07:15:12Z","timestamp":1317885312000},"page":"229-237","source":"Crossref","is-referenced-by-count":30,"title":["Gene\u2010by\u2010environment effect of house dust mite on purinergic receptor P2Y12 (<i>P2RY12<\/i>) and lung function in children with asthma"],"prefix":"10.1111","volume":"42","author":[{"given":"S.","family":"Bunyavanich","sequence":"first","affiliation":[{"name":"Channing Laboratory Department of Medicine Brigham and Women's Hospital Boston MA USA"},{"name":"Division of Rheumatology, Immunology, and Allergy Department of Medicine Brigham and Women's Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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