{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:00:38Z","timestamp":1753891238526,"version":"3.41.2"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Acne vulgaris, a chronic inflammatory skin condition predominantly seen in teenagers, impacts more than 640 million people worldwide. The potential use of lipid-lowering medications as a treatment for acne vulgaris remains underexplored. This study seeks to investigate the impact of lipid-lowering therapies on the risk of developing acne vulgaris using two-sample Mendelian randomization (MR) analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>The two-sample MR method was employed for analysis, and information on lipid-lowering drugs was obtained from the DrugBank and ChEMBL databases. The summary data for blood low-density lipoprotein (LDL) and triglycerides were sourced from the Global Lipids Genetics Consortium, while genome-wide association studies (GWAS) summary data for acne vulgaris were obtained from the FinnGen database. Heterogeneity was examined using the Q-test, horizontal pleiotropy was assessed using MR-Presso, and the robustness of analysis results was evaluated using leave-one-out analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The MR analysis provided robust evidence for an association between lowering LDL cholesterol through two drug targets and acne vulgaris, with PCSK9 showing an odds ratio (OR) of 1.782 (95%CI: 1.129\u20132.812, <jats:italic>p<\/jats:italic>\u2009=\u20090.013) and LDL receptor (LDLR) with an OR of 1.581 (95%CI: 1.071\u20132.334, <jats:italic>p<\/jats:italic>\u2009=\u20090.021). Similarly, targeting the lowering of triglycerides through lipoprotein lipase (LPL) was significantly associated with an increased risk of acne vulgaris, indicated by an OR of 1.607 (95%CI: 1.124\u20132.299, <jats:italic>p<\/jats:italic>\u2009=\u20090.009).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The current MR study presented suggestive evidence of a positive association between drugs targeting three genes (PCSK9, LDLR, and LPL) to lower lipids and a reduced risk of acne vulgaris.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1385948","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T19:29:43Z","timestamp":1718134183000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing lipid-lowering drugs as potential treatment for acne vulgaris: a Mendelian randomization study"],"prefix":"10.3389","volume":"11","author":[{"given":"Man","family":"Fang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/S0140-6736(11)60321-8","article-title":"Acne vulgaris","volume":"379","author":"Williams","year":"2012","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e109","DOI":"10.3928\/19382359-20200211-01","article-title":"Acne vulgaris: treatment made easy for the primary care physician","volume":"49","author":"Berry","year":"2020","journal-title":"Pediatr Ann"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1080\/09546634.2019.1654075","article-title":"Acne vulgaris: new evidence in pathogenesis and future modalities of treatment","volume":"32","author":"Hazarika","year":"2021","journal-title":"J Dermatolog Treat"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/S0095-4543(21)01337-3","article-title":"Acne vulgaris","volume":"16","author":"Wilson","year":"1989","journal-title":"Prim Care"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.jaad.2020.02.040","article-title":"Acne vulgaris and risk of depression and anxiety: a meta-analytic review","volume":"83","author":"Samuels","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1067\/mjd.2003.618","article-title":"Management of acne: a report from a global Alliance to improve outcomes in acne","volume":"49","author":"Gollnick","year":"2003","journal-title":"J Am Acad Dermatol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/molecules21081063","article-title":"Treatment modalities for acne","volume":"21","author":"Fox","year":"2016","journal-title":"Molecules"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.12688\/f1000research.15659.1","article-title":"Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne","volume":"7","author":"Platsidaki","year":"2018","journal-title":"F1000Res"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/1346-8138.12761","article-title":"Acne patients frequently associated with abnormal plasma lipid profile","volume":"42","author":"Jiang","year":"2015","journal-title":"J Dermatol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.cca.2022.06.012","article-title":"Untargeted metabolomics analysis of the plasma metabolic signature of moderate-to-severe acne","volume":"533","author":"Yu","year":"2022","journal-title":"Clin Chim Acta"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/jrsm.1346","article-title":"Meta-analysis and Mendelian randomization: a review","volume":"10","author":"Bowden","year":"2019","journal-title":"Res Synth Methods"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"10","DOI":"10.7554\/eLife.73873","article-title":"Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study","volume":"10","author":"Huang","year":"2021","journal-title":"eLife"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1111\/liv.15566","article-title":"Association between antihypertensive drugs and hepatocellular carcinoma: a trans-ancestry and drug-target Mendelian randomization study","volume":"43","author":"Wang","year":"2023","journal-title":"Liver Int"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1038\/ng.2797","article-title":"Discovery and refinement of loci associated with lipid levels","volume":"45","author":"Willer","year":"2013","journal-title":"Nat Genet"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/ng.3396","article-title":"A comprehensive 1,000 genomes-based genome-wide association meta-analysis of coronary artery disease","volume":"47","author":"Nikpay","year":"2015","journal-title":"Nat Genet"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"R89","DOI":"10.1093\/hmg\/ddu328","article-title":"Mendelian randomization: genetic anchors for causal inference in epidemiological studies","volume":"23","author":"Davey Smith","year":"2014","journal-title":"Hum Mol Genet"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1093\/ije\/dyq151","article-title":"Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants","volume":"40","author":"Pierce","year":"2011","journal-title":"Int J Epidemiol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"f2634","DOI":"10.1136\/bmj.f2634","article-title":"Acne vulgaris","volume":"346","author":"Dawson","year":"2013","journal-title":"BMJ"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1111\/ijd.16220","article-title":"What is new in adult acne for the last 2\u2009years: focus on acne pathophysiology and treatments","volume":"61","author":"Dagnelie","year":"2022","journal-title":"Int J Dermatol"},{"key":"ref20","first-page":"94","article-title":"Acne vulgaris in the United States: a descriptive epidemiology","volume":"86","author":"Yentzer","year":"2010","journal-title":"Cutis"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1136\/bmj.38987.606701.80","article-title":"Acne","volume":"333","author":"Purdy","year":"2006","journal-title":"BMJ"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e015354","DOI":"10.1136\/bmjopen-2016-015354","article-title":"The prevalence of acne in mainland China: a systematic review and meta-analysis","volume":"7","author":"Li","year":"2017","journal-title":"BMJ Open"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.det.2011.11.001","article-title":"Quality of life measures for acne patients","volume":"30","author":"Barnes","year":"2012","journal-title":"Dermatol Clin"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"S225","DOI":"10.1542\/peds.2019-2056L","article-title":"Current issues in the treatment of acne vulgaris","volume":"145","author":"Habeshian","year":"2020","journal-title":"Pediatrics"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.det.2011.09.001","article-title":"Acne vulgaris: pathogenesis, treatment, and needs assessment","volume":"30","author":"Knutsen-Larson","year":"2012","journal-title":"Dermatol Clin"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1111\/ced.14239","article-title":"Acne treatments: future trajectories","volume":"45","author":"Dessinioti","year":"2020","journal-title":"Clin Exp Dermatol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/S0031-3955(16)38158-5","article-title":"Acne vulgaris. Pathogenesis and treatment","volume":"38","author":"Winston","year":"1991","journal-title":"Pediatr Clin N Am"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"5754","DOI":"10.1038\/s41598-020-62715-3","article-title":"Systematic review of the epidemiology of acne vulgaris","volume":"10","author":"Heng","year":"2020","journal-title":"Sci Rep"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.clindermatol.2017.09.006","article-title":"Acne vulgaris: the metabolic syndrome of the pilosebaceous follicle","volume":"36","author":"Melnik","year":"2018","journal-title":"Clin Dermatol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"7053","DOI":"10.3390\/ijms24087053","article-title":"Lipid alterations and metabolism disturbances in selected inflammatory skin diseases","volume":"24","author":"Nowowiejska","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1111\/jocd.14009","article-title":"Consistency changes of potential lipid markers in acne patients of different ages and their role in acne pathogenesis","volume":"20","author":"Chen","year":"2021","journal-title":"J Cosmet Dermatol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"eabo2787","DOI":"10.1126\/sciimmunol.abo2787","article-title":"TREM2 macrophages induced by human lipids drive inflammation in acne lesions","volume":"7","author":"do","year":"2022","journal-title":"Sci Immunol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/978-1-4615-4857-7_27","article-title":"Dermatomyositis and drugs","volume":"455","author":"Dourmishev","year":"1999","journal-title":"Adv Exp Med Biol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1007\/s001050050213","article-title":"Antilipemic drug-induced skin manifestations","volume":"46","author":"Proksch","year":"1995","journal-title":"Hautarzt"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"Cd003697","DOI":"10.1002\/14651858.CD003697.pub2","article-title":"Statins and fibrates for preventing melanoma","volume":"2014","author":"Dellavalle","year":"2005","journal-title":"Cochrane Database Syst Rev"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"2515","DOI":"10.1194\/jlr.R026658","article-title":"The PCSK9 decade","volume":"53","author":"Lambert","year":"2012","journal-title":"J Lipid Res"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/s41569-018-0107-8","article-title":"PCSK9 inhibitors: clinical evidence and implementation","volume":"16","author":"Sabatine","year":"2019","journal-title":"Nat Rev Cardiol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"E271","DOI":"10.1152\/ajpendo.90920.2008","article-title":"Lipoprotein lipase: from gene to obesity","volume":"297","author":"Wang","year":"2009","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"D388","DOI":"10.2741\/goldberg","article-title":"Lipoprotein lipase: physiology, biochemistry, and molecular biology","volume":"6","author":"Goldberg","year":"2001","journal-title":"Front Biosci"},{"key":"ref40","first-page":"19","article-title":"Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis","volume":"85","author":"Go","year":"2012","journal-title":"Yale J Biol Med"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1001\/jama.2017.17219","article-title":"Mendelian randomization","volume":"318","author":"Emdin","year":"2017","journal-title":"JAMA"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1385948\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T19:29:48Z","timestamp":1718134188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1385948\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,6]]},"references-count":41,"alternative-id":["10.3389\/fmed.2024.1385948"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2024.1385948","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2024,6,6]]},"article-number":"1385948"}}