{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T17:20:14Z","timestamp":1762190414516,"version":"build-2065373602"},"reference-count":37,"publisher":"S. Karger AG","issue":"11","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"abstract":"<jats:p>Introduction: TXK regulates IFN-\u03b3 expression and T-helper (Th)1 cell-mediated inflammation that underlies the development of neutrophilic asthma; however, its implication in asthma remains uncertain. This study aimed to functionally characterize the role of TXK single nucleotide polymorphism (SNP) in the development of asthma. Methods: This study is part of an ongoing Singapore\/Malaysia Cross-Sectional Genetics and Epidemiological Study (SMCSGES). In a SMCSGES sub-cohort (n = 658), we assessed the associations of TXK mRNA expression with asthma phenotype, SNP genotype, and the mRNA expression of IFN-\u03b3 and IL23A in peripheral blood mononuclear cell (PBMC). Genetic associations between TXK variants and asthma were investigated in a case-control sub-cohort of SMCSGES (n = 2,407). The functional roles of asthma-associated TXK variants in regulating promoter activity were evaluated by in vitro promoter luciferase assay in THP-1 cells. Results: We identified significant associations of upregulated TXK transcript expression with increased asthma risk (p &lt; 0.05) and the increased transcript expressions of both IFN-\u03b3 (p &lt; 0.0001) and IL23A (p &lt; 0.0001) in PBMC. The major allele \u201cT\u201d of tag-SNP rs2661532 was significantly associated with increased TXK mRNA expression compared to the \u201cC\u201d allele (false discovery rate-adjusted p &lt; 0.05). The \u201cT\u201d allele of rs2661532 was also significantly associated with a higher risk of asthma (p = 0.0346, odds ratio = 1.171, 95% confidence interval = 1.011\u20131.357). The in vitro promoter luciferase assay showed the major alleles of rs6819804 and rs74513879 (tagged by rs2661532) resulted in higher promoter activity of the TXK gene (p &lt; 0.05). Conclusion: This study identified multiple TXK functional variants associated with asthma by regulating the transcript expression of TXK and downstream Th1 and Th17 cell-mediated inflammatory pathways. These findings suggested that TXK functional variants might be involved in the development of neutrophilic asthma.<\/jats:p>","DOI":"10.1159\/000544798","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T12:00:51Z","timestamp":1739966451000},"page":"1009-1021","source":"Crossref","is-referenced-by-count":0,"title":["TXK Functional Variants Contribute to Asthma by Regulating Th1 and Th17 Cytokine Pathways"],"prefix":"10.1159","volume":"186","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-1706","authenticated-orcid":false,"given":"Yang Yie","family":"Sio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terence Yin 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Tim","family":"Chew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00309-2020"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11041226"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.11.020"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/879783"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2023.2125380"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1608969"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3390\/children7120286"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.2.1498"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.8.1147"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.5.2365"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03249.x"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.3121\/cmr.4.2.147"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1111\/all.12364"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2022.100722"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2022.100704"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2023.100757"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.95.08030483"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2156-11-36"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197177"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1193"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.302"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bax028"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz1062"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.07.009"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.614891"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.08.038"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-57592-9"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1159\/000530960"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13883"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1111\/all.15386"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1159\/000530393"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1159\/000540686"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2016-0162"}],"container-title":["International 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