{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:02:38Z","timestamp":1784916158668,"version":"3.55.0"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Mahidol University Fund for New Discovery and Frontier Research"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Type 2-high airway inflammation in adults with asthma is heavily driven by the cytokines interleukin (IL)-4, IL-5, and IL-13. While genetic variations in these cytokines are known to influence asthma pathogenesis, their specific impacts on clinically relevant phenotypes remain to be fully elucidated. This study aimed to investigate the associations between inflammatory cytokine gene polymorphisms, clinical asthma phenotypes, inflammation cell subtypes, and lung function\n                    <jats:bold>.<\/jats:bold>\n                    A cross-sectional study was conducted involving 125 adults with asthma. Genotyping was performed for the following single-nucleotide polymorphisms (SNPs):\n                    <jats:italic>IL33<\/jats:italic>\n                    (rs1342326, rs3939286),\n                    <jats:italic>IL4<\/jats:italic>\n                    (rs2243250, rs2243248),\n                    <jats:italic>IL5<\/jats:italic>\n                    rs2069812, and\n                    <jats:italic>IL13<\/jats:italic>\n                    (rs20541, rs1800925). Clinical evaluations included lung function, blood eosinophils, type 2 innate lymphoid cells (ILC2s), Th2 cells, cytokine levels, and specific IgE. The\n                    <jats:italic>IL4<\/jats:italic>\n                    rs2243248 TT genotype was associated with higher TNF-\u03b1 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.038), while the\n                    <jats:italic>IL13<\/jats:italic>\n                    rs1800925 polymorphism was associated with increased Th2 cell counts (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.025). Notably,\n                    <jats:italic>IL5<\/jats:italic>\n                    rs2069812 was strongly associated with blood eosinophilia (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and reduced lung function. Linear regression revealed a significant gene-dose effect of IL-5 rs2069812 T allele, which correlated with an increase in log\n                    <jats:sub>10<\/jats:sub>\n                    eosinophils (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u20090.207,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and a decrease in post-bronchodilator FEV1% (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u2009\u22127.38,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.014). Furthermore, the\n                    <jats:italic>IL5<\/jats:italic>\n                    rs2069812 and\n                    <jats:italic>IL13<\/jats:italic>\n                    rs1800925 variants significantly increased the risk of blood eosinophilia (Prevalence Ratio [PR] = 2.59,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and fixed airflow obstruction (PR\u2009=\u20091.81,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.039), respectively. The\n                    <jats:italic>IL5<\/jats:italic>\n                    rs2069812 and\n                    <jats:italic>IL13<\/jats:italic>\n                    rs1800925 polymorphisms serve as key genetic determinants of persistent blood eosinophilia and fixed airflow obstruction, respectively. Both variants significantly contribute to the severity of airflow limitation in adult asthma, highlighting their potential as biomarkers for precision phenotyping.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0354597","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:39:08Z","timestamp":1784914748000},"page":"e0354597","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["IL5 rs2069812 and IL13 rs1800925 Genetic variants as key determinants of clinically relevant asthma phenotypes"],"prefix":"10.1371","volume":"21","author":[{"given":"Pattara","family":"Kanoksing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apichaya","family":"Puangpetch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theerasuk","family":"Kawamatawong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thatchathum","family":"Kuttiyod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kantapat","family":"Simmalee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Frutos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8013-6204","authenticated-orcid":true,"given":"Putthapoom","family":"Lumjiaktase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"issue":"10258","key":"pone.0354597.ref001","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"396","year":"2020","journal-title":"Lancet"},{"issue":"5","key":"pone.0354597.ref002","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22052412","article-title":"Genetics and epigenetics in asthma","volume":"22","author":"P Ntontsi","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0354597.ref003","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12948-021-00146-9","article-title":"Defining type 2 asthma and patients eligible for dupilumab in Italy: a biomarker-based analysis","volume":"19","author":"GW Canonica","year":"2021","journal-title":"Clin Mol Allergy"},{"key":"pone.0354597.ref004","unstructured":"Asthma GIF. Global strategy for asthma management and prevention. 2023."},{"issue":"1","key":"pone.0354597.ref005","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/s12881-020-01169-w","article-title":"Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications","volume":"21","author":"D Imani","year":"2020","journal-title":"BMC Med Genet"},{"issue":"12","key":"pone.0354597.ref006","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1046\/j.1365-2222.2000.00983.x","article-title":"Association between a C+33T polymorphism in the IL-4 promoter region and total serum IgE levels","volume":"30","author":"I Suzuki","year":"2000","journal-title":"Clin Exp Allergy"},{"key":"pone.0354597.ref007","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.2147\/JAA.S429981","article-title":"Interleukin-4 (C590T) gene polymorphism in association with asthma severity","volume":"16","author":"M Al-Ahmad","year":"2023","journal-title":"J Asthma Allergy"},{"issue":"2","key":"pone.0354597.ref008","article-title":"Effects of polymorphisms -1112C\/T and 2044A\/G in interleukin-13 gene on asthma risk: a meta-analysis","volume":"8","author":"W Nie","year":"2013","journal-title":"PLOS ONE"},{"issue":"3","key":"pone.0354597.ref009","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1067\/mai.2000.104940","article-title":"A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children","volume":"105","author":"PE Graves","year":"2000","journal-title":"J Allergy Clin Immunol"},{"issue":"3","key":"pone.0354597.ref010","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.resinv.2013.02.003","article-title":"Association of IL-13 gene polymorphisms with airway hyperresponsiveness in a Japanese adult asthmatic population","volume":"51","author":"Y Utsumi","year":"2013","journal-title":"Respir Investig"},{"issue":"3","key":"pone.0354597.ref011","doi-asserted-by":"crossref","first-page":"156","DOI":"10.4103\/bbrj.bbrj_90_19","article-title":"Specific IL-5 snp is associated with high serum IL-5 levels and higher eosinophil counts among iraqi asthmatic children","volume":"3","author":"R Hameed","year":"2019","journal-title":"Biomed Biotechnol Res J"},{"issue":"4","key":"pone.0354597.ref012","doi-asserted-by":"crossref","first-page":"264","DOI":"10.55133\/eji.280427","article-title":"Serum interleukin 33 levels and single nucleotide polymorphism rs1929992 in Egyptian patients with chronic asthma","volume":"28","author":"RA Rabea","year":"2021","journal-title":"The Egyptian Journal of Immunology"},{"issue":"1","key":"pone.0354597.ref013","first-page":"24","article-title":"The validity and reliability of the Thai version of the asthma control test","volume":"42","author":"N Niyatiwatchanchai","year":"2024","journal-title":"Asian Pac J Allergy Immunol"},{"issue":"11","key":"pone.0354597.ref014","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1164\/rccm.202310-1773OC","article-title":"Severity of Airflow Obstruction Based on FEV1\/FVC Versus FEV1Percent Predicted in the General U.S. Population","volume":"210","author":"H Backman","year":"2024","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"issue":"3","key":"pone.0354597.ref015","doi-asserted-by":"crossref","DOI":"10.3390\/vaccines11030531","article-title":"Special Issue on \u201cAsthma and Allergic Inflammation\u201d","volume":"11","author":"C Pelaia","year":"2023","journal-title":"Vaccines"},{"key":"pone.0354597.ref016","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/S0091-6749(97)70276-8","article-title":"The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4+ or CD8+ T cells","volume":"100","author":"J Punnonen","year":"1997","journal-title":"J Allergy Clin Immunol"},{"key":"pone.0354597.ref017","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.3389\/fphys.2019.01514","article-title":"Interleukin-5 in the Pathophysiology of Severe Asthma","volume":"10","author":"C Pelaia","year":"2019","journal-title":"Front Physiol"},{"key":"pone.0354597.ref018","doi-asserted-by":"crossref","DOI":"10.3402\/ecrj.v1.25535","article-title":"Exploring the origins of asthma: Lessons from twin studies","volume":"1","author":"SF Thomsen","year":"2014","journal-title":"Eur Clin Respir J"},{"issue":"9","key":"pone.0354597.ref019","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.21037\/tp-21-419","article-title":"Polymorphisms in the interleukin 4 promoter -589C\/T gene and the risk of asthma: a systematic review and meta-analysis","volume":"10","author":"L Zhu","year":"2021","journal-title":"Transl Pediatr"},{"issue":"9","key":"pone.0354597.ref020","doi-asserted-by":"crossref","first-page":"5224","DOI":"10.4049\/jimmunol.162.9.5224","article-title":"IL-4 inhibits the production of TNF-alpha and IL-12 by STAT6-dependent and -independent mechanisms","volume":"162","author":"MK Levings","year":"1999","journal-title":"J Immunol"},{"issue":"3","key":"pone.0354597.ref021","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.coph.2007.03.001","article-title":"TNF-alpha in asthma","volume":"7","author":"M Berry","year":"2007","journal-title":"Curr Opin Pharmacol"},{"issue":"2","key":"pone.0354597.ref022","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1159\/000342420","article-title":"Tumor necrosis factor alpha-mediated asthma?","volume":"160","author":"T Nabe","year":"2013","journal-title":"Int Arch Allergy Immunol"},{"issue":"1","key":"pone.0354597.ref023","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/s12881-020-01169-w","article-title":"Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications","volume":"21","author":"D Imani","year":"2020","journal-title":"BMC Med Genet"},{"issue":"2","key":"pone.0354597.ref024","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nri.2017.118","article-title":"T(H)2 cell development and function","volume":"18","author":"JA Walker","year":"2018","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"pone.0354597.ref025","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/ni.3294","article-title":"Group 2 innate lymphoid cells license dendritic cells to potentiate memory TH2 cell responses","volume":"17","author":"TYF Halim","year":"2016","journal-title":"Nat Immunol"},{"issue":"2","key":"pone.0354597.ref026","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4168\/aair.2010.2.2.134","article-title":"IL-13 Gene Polymorphisms are Associated With Rhinosinusitis and Eosinophilic Inflammation in Aspirin Intolerant Asthma","volume":"2","author":"NS Palikhe","year":"2010","journal-title":"Allergy Asthma Immunol Res"},{"issue":"12","key":"pone.0354597.ref027","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1093\/intimm\/dxp102","article-title":"IL-5- and eosinophil-mediated inflammation: from discovery to therapy","volume":"21","author":"T Kouro","year":"2009","journal-title":"Int Immunol"},{"key":"pone.0354597.ref028","doi-asserted-by":"crossref","first-page":"105875","DOI":"10.1016\/j.rmed.2020.105875","article-title":"Elevated eosinophils, IL5 and IL8 in induced sputum in asthma patients with accelerated FEV1 decline","volume":"162","author":"M Marc-Malovrh","year":"2020","journal-title":"Respir Med"},{"key":"pone.0354597.ref029","doi-asserted-by":"crossref","unstructured":"Hameed R, Ahmed M, Abood HA. Impact of IL-5C-703T and IL-5 receptor AlphaG-80A polymorphisms on immunological parameter in treated asthmatic children. 2019;2:600.","DOI":"10.4103\/bbrj.bbrj_13_20"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0354597","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:39:14Z","timestamp":1784914754000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0354597"}},"subtitle":[],"editor":[{"given":"Mizanur","family":"Rahman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0354597","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}