{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:43:26Z","timestamp":1790729006031,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Current knowledge of gout centers on hyperuricemia. Relatively little is known regarding the pathogenesis of gouty inflammation. To investigate the epigenetic background of gouty inflammation independent of hyperuricemia and its relationship to genetics, 69 gout patients and 1455 non-gout controls were included. Promoter-wide methylation was profiled with EPIC array. Whole-genome sequencing data were included for genetic and methylation quantitative trait loci (meQTL) analyses and causal inference tests. Identified loci were subjected to co-methylation analysis and functional localization with DNase hypersensitivity and histone marks analysis. An expression database was queried to clarify biologic functions of identified loci. A transcription factor dataset was integrated to identify transcription factors coordinating respective expression. In total, seven CpG loci involved in interleukin-1\u03b2 production survived genetic\/meQTL analyses, or causal inference tests. None had a significant relationship with various metabolic traits. Additional analysis suggested gouty inflammation, instead of hyperuricemia, provides the link between these CpG sites and gout. Six (PGGT1B, INSIG1, ANGPTL2, JNK1, UBAP1, and RAPTOR) were novel genes in the field of gout. One (CNTN5) was previously associated with gouty inflammation. Transcription factor mapping identified several potential transcription factors implicated in the link between differential methylation, interleukin-1\u03b2 production, and gouty inflammation. In conclusion, this study revealed several novel genes specific to gouty inflammation and provided enhanced insight into the biological basis of gouty inflammation.<\/jats:p>","DOI":"10.3390\/ijms21134702","type":"journal-article","created":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T02:44:25Z","timestamp":1593657865000},"page":"4702","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Systemic Investigation of Promoter-wide Methylome and Genome Variations in Gout"],"prefix":"10.3390","volume":"21","author":[{"given":"Chia-Chun","family":"Tseng","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man Chun","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Ting","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Chen","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Diagnosis of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeng-Hsien","family":"Yen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"},{"name":"Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Department of Biological Science and Technology, National Chiao-Tung University, Hsinchu 30010, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Jen","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, Health and Leisure Studies, National University of Kaohsiung, Kaohsiung 81148, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s13075-018-1633-9","article-title":"Gout prevalence and predictors of urate-lowering therapy use: Results from a population-based study","volume":"20","author":"Pisaniello","year":"2018","journal-title":"Arthritis Res. 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