{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:15:18Z","timestamp":1785521718030,"version":"3.56.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81460153"],"award-info":[{"award-number":["81460153"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82002276"],"award-info":[{"award-number":["82002276"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100015310","name":"Natural Science Foundation of Xinjiang","doi-asserted-by":"publisher","award":["2020D01C263"],"award-info":[{"award-number":["2020D01C263"]}],"id":[{"id":"10.13039\/501100015310","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015310","name":"Natural Science Foundation of Xinjiang","doi-asserted-by":"publisher","award":["2022D01C756"],"award-info":[{"award-number":["2022D01C756"]}],"id":[{"id":"10.13039\/501100015310","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Special fund project of youth scientific Research sailing from The First Affiliated Hospital of Xinjiang Medical University","award":["2022-74"],"award-info":[{"award-number":["2022-74"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>The Toll-like receptor (TLR) 4-mediated nuclear factor kappa B (NF-\u03baB) signaling pathway regulates the production of inflammatory factors and plays a key role in the pathogenesis of gouty arthritis. The aim of the present study was to investigate the link among <jats:italic>TLR4 gene<\/jats:italic> polymorphisms at various loci, protein expression, and gouty arthritis susceptibility.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Between 2016 and 2021, a case-control study was used to collect a total of 1207 study subjects, including 317 male patients with gouty arthritis (gout group) and 890 healthy males (control group). The association between gout susceptibility and different genetic models was analyzed by typing three loci of the <jats:italic>TLR4 gene<\/jats:italic> (rs2149356, rs2737191, and rs10759932) using a multiplex point mutation rapid assay, and the association between protein expression and gout was confirmed by measuring TLR4 protein concentrations using enzyme-linked immunosorbent assays (ELISAs).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>In a codominant models AA and AG, the rs2737191 polymorphism in the gout group increased the risk of gout compared to the AA genotype (<jats:italic>OR = 2<\/jats:italic>.<jats:italic>249<\/jats:italic>, <jats:italic>95%CI 1<\/jats:italic>.<jats:italic>010~5<\/jats:italic>.<jats:italic>008<\/jats:italic>), and the risk of gout was higher for those carrying the G allele compared to the A allele (<jats:italic>OR = 2<\/jats:italic>.<jats:italic>227<\/jats:italic>, <jats:italic>95%CI 1<\/jats:italic>.<jats:italic>006~4<\/jats:italic>.<jats:italic>932<\/jats:italic>). TLR4 protein expression was different between the two groups with different locus genotypes. The differences in TLR4 protein expression between the gout group and control group were statistically significant between the following genotypes: the GG and GT genotypes of the rs2149356 polymorphism; the AA and AG genotypes of the rs2737191 polymorphism; and the TT and TC genotypes of the rs10759932 polymorphism(<jats:italic>P<\/jats:italic>&lt;0.05). The <jats:italic>TLR4 protein<\/jats:italic> level in the gout group (19.19\u00b13.09 ng\/ml) was significantly higher than that in the control group (15.85\u00b14.75 ng\/ml).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The AG genotype of the <jats:italic>TLR4 gene<\/jats:italic> rs2737191 polymorphism may be correlated with the development of gouty arthritis. The level of <jats:italic>TLR4 protein<\/jats:italic> expression is significantly higher in patients with gouty arthritis than in controls, and there is a correlation between high TLR4 protein expression and the development of gouty arthritis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0300582","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T17:31:12Z","timestamp":1713893472000},"page":"e0300582","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Correlation analysis of serum TLR4 protein levels and TLR4 gene polymorphisms in gouty arthritis patients"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7464-2776","authenticated-orcid":true,"given":"Lu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4479-4118","authenticated-orcid":true,"given":"Lei","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"issue":"21","key":"pone.0300582.ref001","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1001\/jama.2016.3517","article-title":"Trends in gout and rheumatoid arthritis hospitalizations in the United States, 1993\u20132011","volume":"315","author":"SY Lim","year":"2016","journal-title":"JAMA"},{"issue":"6099","key":"pone.0300582.ref002","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1222794","article-title":"Systematic localization of common disease-associated variation in regulatory DNA","volume":"337","author":"T Maurano M","year":"2012","journal-title":"Sciene"},{"key":"pone.0300582.ref003","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/1471-2474-11-98","article-title":"The prevalence of rheumatic diseases in central Greece: a population survey.","volume":"11","author":"I Anagnostopoulos","year":"2010","journal-title":"BMC Musculoskelet Disord"},{"issue":"1","key":"pone.0300582.ref004","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/acr.21791","article-title":"Body mass index, obesity, and prevalent gout in the United States in 1988\u20131994 and 2007\u20132010[J].","volume":"65","author":"SP Juraschek","year":"2013","journal-title":"Arthritis Care Res"},{"issue":"4","key":"pone.0300582.ref005","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1136\/annrheumdis-2013-204463","article-title":"Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study[J]","volume":"74","author":"CF Kuo","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"pone.0300582.ref006","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1002\/art.40807","article-title":"Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 20072016.","volume":"71","author":"M Chen-Xu","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"pone.0300582.ref007","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.semarthrit.2016.08.006","article-title":"The rising prevalence and incidence of gout in British Columbia, Canada: Population-based trends from 2000 to 2012","volume":"46","author":"SK Rai","year":"2017","journal-title":"Semin Arthritis Rheum"},{"issue":"31","key":"pone.0300582.ref008","first-page":"7807","article-title":"Epidemiological survey of gout in Shenzhen","volume":"8","author":"X. 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