{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:31:50Z","timestamp":1759336310869,"version":"3.41.2"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T00:00:00Z","timestamp":1659225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014759","name":"Medical Scientific Research Foundation of Zhejiang Province, China","doi-asserted-by":"publisher","award":["2022KY328","2020KY268"],"award-info":[{"award-number":["2022KY328","2020KY268"]}],"id":[{"id":"10.13039\/501100014759","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The purpose of this study was to identify biomarkers for the diagnosis of gout in Chinese Han males using methylation microarray profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We screened for differentially methylated genes (DMGs) in gout using a methylation microarray and analyzed the functions of the DMGs using gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. We verified gene methylation levels by pyrosequencing and protein levels by enzyme\u2010linked immunosorbent assays (ELISAs). Statistical analyses were performed using SPSS. Two\u2010sided <jats:italic>p<\/jats:italic> values &lt;0.05 were deemed to be statistically significant for all analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 20,426 significant differential methylation sites (5719 high\u2010methylation sites and 14,707 low\u2010methylation sites). Bioinformatics analysis showed that the DMGs were mainly involved in 43 biological functions, 13 cellular components, 18 molecular functions, and 35 KEGG pathways. We selected <jats:italic>opioid receptor delta 1<\/jats:italic> (<jats:italic>OPRD1<\/jats:italic>) for verification of methylation levels between 50 gout patients and 50 controls. The methylation levels of <jats:italic>OPRD1<\/jats:italic> (Chr1:29,139,121) were significantly lower in the gout group (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), while OPRD1 protein levels were significantly higher in the gout group (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In addition, the AUC of the combination of <jats:italic>OPRD1<\/jats:italic> (Chr1:29,139,121) methylation and OPRD1 protein levels was 0.796 (0.710, 0.883) with a high sensitivity of 82% and a specificity of 68% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The combination of <jats:italic>OPRD1<\/jats:italic> (Chr1:29,139,121) hypomethylation and high levels of OPRD1 protein is a potential biomarker for gout diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24634","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:09:30Z","timestamp":1659312570000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypomethylation of the <i>opioid receptor delta 1<\/i> gene combined with high opioid receptor delta 1 protein levels indicates increased risk of gout"],"prefix":"10.1002","volume":"36","author":[{"given":"Ying","family":"Ying","sequence":"first","affiliation":[{"name":"Department of Rheumatology Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No. 2 Hospital)  Ningbo Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoke","family":"Li","sequence":"additional","affiliation":[{"name":"Medical School, Ningbo University  Ningbo Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2874-1516","authenticated-orcid":false,"given":"Yong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No. 2 Hospital)  Ningbo Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,31]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1","article-title":"One year in 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