{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T20:31:23Z","timestamp":1784925083704,"version":"3.55.0"},"reference-count":83,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NICHD 5R01HD086911"],"award-info":[{"award-number":["NICHD 5R01HD086911"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The melanocortin receptors are G-protein-coupled receptors, which are essential components of the hypothalamic\u2013pituitary\u2013adrenal axis, and they mediate the actions of melanocortins (melanocyte-stimulating hormones: \u03b1-MSH, \u03b2-MSH, and \u03b3-MSH) as well as the adrenocorticotropin hormone (ACTH) in skin pigmentation, adrenal steroidogenesis, and stress response. Three melanocortin receptor genes (MC1R, MC2R, and MC5R) contribute to the risk of major depressive disorder (MDD), and one melanocortin receptor gene (MC4R) contributes to the risk of type 2 diabetes (T2D). MDD increases T2D risk in drug-na\u00efve patients; thus, MDD and T2D commonly coexist. The five melanocortin receptor genes might confer risk for both disorders. However, they have never been investigated jointly to evaluate their potential contributing roles in the MDD-T2D comorbidity, specifically within families. In 212 Italian families with T2D and MDD, we tested 11 single nucleotide polymorphisms (SNPs) in the MC1R gene, 9 SNPs in MC2R, 3 SNPs in MC3R, 4 SNPs in MC4R, and 2 SNPs in MC5R. The testing used 2-point parametric linkage and linkage disequilibrium (LD) (i.e., association) analysis with four models (dominant with complete penetrance (D1), dominant with incomplete penetrance (D2), recessive with complete penetrance (R1), and recessive with incomplete penetrance (R2)). We detected significant (p \u2264 0.05) linkage and\/or LD (i.e., association) to\/with MDD for one SNP in MC2R (rs111734014) and one SNP in MC5R (rs2236700), and to\/with T2D for three SNPs in MC1R (rs1805007 and rs201192930, and rs2228479), one SNP in MC2R (rs104894660), two SNPs in MC3R (rs3746619 and rs3827103), and one SNP in MC4R genes (Chr18-60372302). The linkage\/LD\/association was significant across different linkage patterns and different modes of inheritance. All reported variants are novel in MDD and T2D. This is the first study to report risk variants in MC1R, MC2R, and MC3R genes in T2D. MC2R and MC5R genes are replicated in MDD, with one novel variant each. Within our dataset, only the MC2R gene appears to confer risk for both MDD and T2D, albeit with different risk variants. To further clarity the role of the melanocortin receptor genes in MDD-T2D, these findings should be sought among other ethnicities as well.<\/jats:p>","DOI":"10.3390\/ijms23158350","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T20:49:28Z","timestamp":1659041368000},"page":"8350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Implication of Melanocortin Receptor Genes in the Familial Comorbidity of Type 2 Diabetes and Depression"],"prefix":"10.3390","volume":"23","author":[{"given":"Mutaz","family":"Amin","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), US14-Orphanet, 75014 Paris, France"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, Al-Neelain University, Khartoum 11121, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6188-1388","authenticated-orcid":false,"given":"Jurg","family":"Ott","sequence":"additional","affiliation":[{"name":"Laboratory of Statistical Genetics, Rockefeller University, New York City, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2334-6421","authenticated-orcid":false,"given":"Rongling","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Statistics and Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6056-4244","authenticated-orcid":false,"given":"Teodor T.","family":"Postolache","sequence":"additional","affiliation":[{"name":"Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 19, Denver, CO 80246, USA"},{"name":"Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Denver, CO 80246, USA"},{"name":"Mental Illness Research Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 5, VA Capitol Health Care Network, Baltimore, MD 21090, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Gragnoli","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"},{"name":"Division of Endocrinology, Department of Medicine, Creighton University School of Medicine, Omaha, NE 68124, USA"},{"name":"Molecular Biology Laboratory, Bios Biotech Multi-Diagnostic Health Center, 00197 Rome, Italy"},{"name":"Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1016\/j.bbadis.2017.08.001","article-title":"Melanocortin receptors","volume":"1863","author":"Tao","year":"2017","journal-title":"Biochim. 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