{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:46:14Z","timestamp":1790178374183,"version":"4.1.0"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T00:00:00Z","timestamp":1600041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T00:00:00Z","timestamp":1600041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R03DA039745, R01DA038632, R01DA047063, R01DA047820"],"award-info":[{"award-number":["R03DA039745, R01DA038632, R01DA047063, R01DA047820"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Epigenet"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cocaine use accelerates human immunodeficiency virus (HIV) progression and worsens HIV outcomes. We assessed whether DNA methylation in blood mediates the association between cocaine use and HIV severity in a veteran population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed 1435 HIV-positive participants from the Veterans Aging Cohort Study Biomarker Cohort (VACS-BC). HIV severity was measured by the Veteran Aging Cohort Study (VACS) index. We assessed the effect of cocaine use on VACS index and mortality among the HIV-positive participants. We selected candidate mediators that were associated with both persistent cocaine use and VACS index by epigenome-wide association (EWA) scans at a liberal\n                      <jats:italic>p<\/jats:italic>\n                      value cutoff of 0.001. Mediation analysis of the candidate CpG sites between cocaine\u2019s effect and the VACS index was conducted, and the joint mediation effect of multiple CpGs was estimated. A two-step epigenetic Mendelian randomization (MR) analysis was conducted as validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      More frequent cocaine use was significantly associated with a higher VACS index (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 1.00,\n                      <jats:italic>p<\/jats:italic>\n                      = 2.7E\u221204), and cocaine use increased the risk of 10-year mortality (hazard ratio = 1.10,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.011) with adjustment for confounding factors. Fifteen candidate mediator CpGs were selected from the EWA scan. Twelve of these CpGs showed significant mediation effects, with each explaining 11.3\u201329.5% of the variation. The mediation effects for 3 of the 12 CpGs were validated by the two-step epigenetic MR analysis. The joint mediation effect of the 12 CpGs accounted for 47.2% of cocaine\u2019s effect on HIV severity. Genes harboring these 12 CpGs are involved in the antiviral response (\n                      <jats:italic>IFIT3<\/jats:italic>\n                      ,\n                      <jats:italic>IFITM1<\/jats:italic>\n                      ,\n                      <jats:italic>NLRC5<\/jats:italic>\n                      ,\n                      <jats:italic>PLSCR1<\/jats:italic>\n                      ,\n                      <jats:italic>PARP9<\/jats:italic>\n                      ) and HIV progression (\n                      <jats:italic>CX3CR1<\/jats:italic>\n                      ,\n                      <jats:italic>MX1<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified 12 DNA methylation CpG sites that appear to play a mediation role in the association between cocaine use and HIV severity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13148-020-00934-1","type":"journal-article","created":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T08:02:53Z","timestamp":1600070573000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["DNA methylation mediates the effect of cocaine use on HIV severity"],"prefix":"10.1186","volume":"12","author":[{"given":"Chang","family":"Shu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C.","family":"Justice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana B.","family":"Hancock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric O.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-7052","authenticated-orcid":false,"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"issue":"1","key":"934_CR1","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1016\/S2352-3018(14)70001-3","volume":"1","author":"M Daskalopoulou","year":"2014","unstructured":"Daskalopoulou M, Rodger A, Phillips AN, et al. 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