{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T23:58:26Z","timestamp":1768003106923,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108\u20102320\u2010B\u2010037\u2010034\u2010MY3"],"award-info":[{"award-number":["MOST 108\u20102320\u2010B\u2010037\u2010034\u2010MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108\u20102410\u2010H\u2010006\u2010046\u2010"],"award-info":[{"award-number":["MOST 108\u20102410\u2010H\u2010006\u2010046\u2010"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108\u20102628\u2010B\u2010037\u2010002\u2010"],"award-info":[{"award-number":["MOST 108\u20102628\u2010B\u2010037\u2010002\u2010"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011645","name":"Kaohsiung Medical University Hospital","doi-asserted-by":"publisher","award":["KMUH108\u20108R60"],"award-info":[{"award-number":["KMUH108\u20108R60"]}],"id":[{"id":"10.13039\/501100011645","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Viral hepatitis is a devastating disease with the risk for cirrhosis and carcinogenicity. Regulatory T cells (Tregs) play important roles in the disease course of viral hepatitis via maintaining the balance between overt\u2010immune responses and viral replications. We hypothesized that genetic polymorphisms of Treg\u2010related genes, such as interleukin\u20102, transforming growth factor\u2010\u03b2 1 (TGF\u2010\u03b21), forkhead box P3 (FOXP3), and adenylyl cyclase type 9 modulate the hosts' immune regulation under circumstances of viral hepatitis. We examined the effect of five single nucleotide polymorphisms (SNPs) of Treg\u2010related genes on the levels of C\u2010reactive protein (CRP) and erythrocyte sedimentation rate (ESR), alanine aminotransferase, and non\u2010invasive hepatic fibrosis marker (Fibrosis\u20104 index) in a total of 138 participants with viral hepatitis. The rs1800469 (a TGF\u2010\u03b21 SNP) GG genotype is associated with higher serum CRP levels, and the rs3761547 (a FOXP3 SNP) C allele in the females is associated with higher ESR levels. Besides, female participants carrying the rs3761547 C allele had a significantly higher Fibrosis\u20104 (FIB\u20104) index than the females carrying the TT genotype, while the rs3761547 C allele had the opposite effect in males. With linear\u2010regression moderation analysis, we found that sex moderated the impact of the FOXP3 SNP on the levels of FIB\u20104, whereas the FOXP3 SNP caused the opposite effect between males and females on the severity of hepatic fibrosis. These results provide evidence for the participation of TGF\u2010\u03b21 and FOXP3 in the inflammatory responses associated with viral hepatitis, where FOXP3 function may be moderated by sex.<\/jats:p>","DOI":"10.1002\/kjm2.12414","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T16:00:40Z","timestamp":1624550440000},"page":"1000-1009","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic polymorphisms of regulatory T cell\u2010related genes modulate systemic inflammation induced by viral hepatitis"],"prefix":"10.1002","volume":"37","author":[{"given":"Hsueh\u2010Hsin","family":"Kao","sequence":"first","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Laboratory Medicine Kaohsiung Medical University Hospital  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5836-1237","authenticated-orcid":false,"given":"Rwei\u2010Ling","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Behavioral Medicine, College of Medicine National Cheng Kung University  Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan\u2010Long","family":"Chuang","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2752-7051","authenticated-orcid":false,"given":"Jee\u2010Fu","family":"Huang","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia\u2010Yen","family":"Dai","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6950-4678","authenticated-orcid":false,"given":"Chun\u2010Hsiang","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology Kaohsiung Medical University Hospital  Kaohsiung Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107053450107"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2009.01081.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0120-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1181"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.739"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01578"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2005.10.005"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.7"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06878"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001405"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02014"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55427-w"},{"key":"e_1_2_6_14_1","first-page":"507\u2010xvii","volume-title":"Introduction to mediation, moderation, and conditional process analysis: a regression\u2010based approach","author":"Hayes AF","year":"2013"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.1.93"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2010.04.021"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00754"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/v1020104"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(2000012)30:12<3516::AID-IMMU3516>3.0.CO;2-S"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2017.06.005"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13601-016-0096-9"},{"issue":"9","key":"e_1_2_6_22_1","first-page":"4635","article-title":"Effects of gene polymorphism and serum levels of IL\u20102 and IL\u20106 on endometriosis","volume":"24","author":"Wang XQ","year":"2020","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022236"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7589"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.9.5149"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030152"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-006-0194-1"},{"issue":"8","key":"e_1_2_6_28_1","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.4049\/jimmunol.145.8.2507","article-title":"Regulation of cytokine\u2010induced human C\u2010reactive protein production by transforming growth factor\u2010beta","volume":"145","author":"Taylor AW","year":"1990","journal-title":"J Immunol"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8702372"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.12742"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2754"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.112.004176"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12862"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.07.006"},{"issue":"6","key":"e_1_2_6_35_1","first-page":"5366","article-title":"Decreased regulatory T\u2010cell frequency and interleukin\u201035 levels in patients with rheumatoid arthritis","volume":"16","author":"Zhang X","year":"2018","journal-title":"Exp Therapeutic Med"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00493"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.619268"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2020.01.007"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0171755"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229345"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/opo.12131"}],"container-title":["The Kaohsiung Journal of Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/kjm2.12414","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/kjm2.12414","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/kjm2.12414","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T12:07:47Z","timestamp":1693224467000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/kjm2.12414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,24]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1002\/kjm2.12414"],"URL":"https:\/\/doi.org\/10.1002\/kjm2.12414","archive":["Portico"],"relation":{},"ISSN":["1607-551X","2410-8650"],"issn-type":[{"value":"1607-551X","type":"print"},{"value":"2410-8650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,24]]},"assertion":[{"value":"2021-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}