{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:01:19Z","timestamp":1788829279365,"version":"build-2803163510"},"reference-count":174,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Melanocortin receptors (MCRs) are responsible for various functions ranging from skin pigmentation, regulation of appetite, stress response and cognition, steroid synthesis, and energy balance to cellular regeneration and immunomodulation. The genetic polymorphism with tissue distribution ranging from the brain, limbic system, and adrenal cortex to neutrophils, monocytes, and macrophages is evident in MCRs. The mutations in MC1R, MC2R, MC3R, and MC4R genes are associated with risk of melanoma, familial glucocorticoid deficiency, obesity, and type 2 diabetes mellitus, respectively. Meanwhile, MC1R, MC2R, and MC5R genes are involved in the risk of major depressive disorder. Melanocortin receptors are involved in different inflammatory disorders, i.e., atopic dermatitis, autoimmune uveitis, sarcoidosis, respiratory diseases, multiple sclerosis, scleroderma, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer\u2019s disease, arthritis, and reperfusion injury. Several newer therapeutic agents related to MCRs have numerous advantages over the current anti-inflammatory drugs, demonstrating therapeutic relevance. Among them, \u03b1-MSH analogs play a role in atopic dermatitis and scleroderma, and MC1R agonist Dersimelagon has shown effectiveness in systemic sclerosis. The FDA has recently approved the repository corticotropin injection (RCI) to treat sarcoidosis. The FDA has also approved various melanocortin agonists, i.e., Bremelanotide, Afamelanotide, and Setmelanotide, for the treatment of hypoactive sexual desire disorder, Erythropoietic protoporphyria, and obesity, due to pro-opiomelanocortin and leptin receptor deficiency, respectively. Therefore, this review aims to summarize the function and genetic polymorphism of melanocortin receptors, regulatory pathways involving MCRs, and the existing evidence of the prime effect of MCRs on inflammatory responses via different mechanisms and their potential therapeutic use in inflammatory diseases.<\/jats:p>","DOI":"10.3390\/diseases13090305","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T14:31:41Z","timestamp":1758033101000},"page":"305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Polymorphism of Melanocortin Receptor Genes\u2014Association with Inflammatory Traits and Diseases"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4106-409X","authenticated-orcid":false,"given":"Mainak","family":"Bardhan","sequence":"first","affiliation":[{"name":"The John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33101, USA"},{"name":"The Dr. John T. Macdonald Foundation, Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayush","family":"Anand","sequence":"additional","affiliation":[{"name":"BP Koirala Institute of Health Sciences, Dharan 56700, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2072-4490","authenticated-orcid":false,"given":"Amaan","family":"Javed","sequence":"additional","affiliation":[{"name":"University College of Medical Sciences, Dilshad Garden, Delhi 110095, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Andrea","family":"Chilo","sequence":"additional","affiliation":[{"name":"UAB Department of Family and Community Medicine and Cahaba Medical Care, Birmingham, AL 35205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nida","family":"Khan","sequence":"additional","affiliation":[{"name":"Jinnah Sindh Medical University, Karachi 75510, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tulika","family":"Garg","sequence":"additional","affiliation":[{"name":"Government Medical College and Hospital, Chandigarh 160030, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arihant","family":"Surana","sequence":"additional","affiliation":[{"name":"St. Vincent Hospital, Worcester, MA 01608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2809-0154","authenticated-orcid":false,"given":"Helen","family":"Huang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Science, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3367-1455","authenticated-orcid":false,"given":"M M","family":"Samim","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore 560030, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Warneford Hospital, Warneford Ln, Headington, Oxford OX3 7JX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinav","family":"Khare","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences, Gorakhpur 273008, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bindu","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Neurology, Apollo Specialty Hospitals, Nellore 524004, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tithishri","family":"Kundu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Manipal Tata Medical College Jamshedpur, Manipal Academy of Higher Education, Manipal 576104, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"586","DOI":"10.2174\/1389450033490858","article-title":"Melanocortins and their receptors and antagonists","volume":"4","author":"Voisey","year":"2003","journal-title":"Curr. 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