{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:21:20Z","timestamp":1787772080492,"version":"build-2784847793"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4]]},"abstract":"Abstract<\/jats:title>\n \n Background:<\/jats:title>\n Obesity is a global epidemic with diverse metabolic outcomes, categorized as metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). Genetic variations in the MC4R gene are known to be key to energy homeostasis, making it a critical candidate for explaining this metabolic heterogeneity.<\/jats:p>\n <\/jats:sec>\n \n Aim:<\/jats:title>\n This study aimed to investigate the genetic basis of metabolically unhealthy obesity (MUHO) in a North Indian population from the Jammu region, specifically focusing on the association between polymorphisms (Single Nucleotide Polymorphisms [SNPs]) within the Melanocortin-4 Receptor (MC4R) gene and the predisposition to MUHO.<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n \n We analyzed a cohort of 846 adult participants from the North Indian population of the Jammu region. The participants were divided into three groups: MUHO (\n N<\/jats:italic>\n = 300), MHO (\n N<\/jats:italic>\n = 246), and metabolically healthy normal weight (MH-NW,\n N<\/jats:italic>\n = 300). Genotyping was performed to assess the association of the two specific MC4R: rs2331841 and rs12970134.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Our findings revealed a statistically significant association between the \u201cA\u201d risk alleles of both MC4R SNPs and an increased predisposition to MUHO. The \u201cA\u201d allele of rs2331841 conferred a 1.75-fold increased risk for MUHO compared to MH-NW (\n P<\/jats:italic>\n = 0.0008) and a 1.42-fold increased risk compared to MHO (\n P<\/jats:italic>\n = 0.02). The \u201cA\u201d allele of rs12970134 showed a 1.60-fold increased risk for MUHO versus MH-NW (\n P<\/jats:italic>\n = 0.005) and a 1.35-fold increased risk versus MHO (\n P<\/jats:italic>\n = 0.057).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n These results indicate that genetic variations in the MC4R gene contribute to the metabolic heterogeneity of obesity. Identifying these specific genetic markers is crucial for early risk stratification and developing personalized preventive strategies against obesity-related metabolic disorders.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/ijabmr.ijabmr_408_25","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:00:37Z","timestamp":1781622037000},"page":"87-91","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Association of Melanocortin-4 Receptor Single Nucleotide Polymorphisms rs2331841 and rs12970134 with Metabolically Unhealthy Obesity in a North Indian Cohort"],"prefix":"10.4103","volume":"16","author":[{"given":"Isar","family":"Sharma","sequence":"first","affiliation":[{"name":"School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kritika","family":"Bakshi","sequence":"additional","affiliation":[{"name":"School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Mahajan","sequence":"additional","affiliation":[{"name":"School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Kapoor","sequence":"additional","affiliation":[{"name":"School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir, India"},{"name":"Institute of Human Genetics, University of Jammu, Jammu, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"R1-20260617","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3803\/EnM.2020.301","article-title":"Metabolically healthy and unhealthy normal weight and obesity","volume":"35","author":"Stefan","year":"2020","journal-title":"Endocrinol Metab (Seoul)"},{"key":"R2-20260617","doi-asserted-by":"crossref","first-page":"924649","DOI":"10.3389\/fphys.2022.924649","article-title":"The harm of metabolically healthy obese and the effect of exercise on their health promotion","volume":"13","author":"Su","year":"2022","journal-title":"Front Physiol"},{"key":"R3-20260617","doi-asserted-by":"crossref","first-page":"4328909","DOI":"10.1155\/2019\/4328909","article-title":"MC4R single nucleotide polymorphisms were associated with metabolically healthy and unhealthy obesity in Chinese northern Han 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metabolism","volume":"293","author":"Podyma","year":"2018","journal-title":"J Biol Chem"},{"key":"R11-20260617","doi-asserted-by":"crossref","first-page":"94","DOI":"10.5603\/MRJ.a2021.0023","article-title":"MC4R polymorphism in rs17782313 influences on insulin resistance","volume":"6","author":"Szywacz","year":"2021","journal-title":"Med Res J"},{"key":"R12-20260617","first-page":"1221","article-title":"Association of the rs17782313, rs17773430 and rs34114122 polymorphisms of\/near MC4R gene with obesity-related biomarkers in a Spanish pediatric cohort","volume":"10","author":"Carrasco-Luna","year":"2023","journal-title":"Children (Basel)"},{"key":"R13-20260617","article-title":"Pharmacogenomics of Anti-Obesity Drugs: A Bioinformatics Approach","author":"de","journal-title":"Research Square"},{"key":"R14-20260617","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/S2213-8587(23)00232-2","article-title":"Precision medicine of obesity as an integral part of type 2 diabetes management \u2013Past, present, and future","volume":"11","author":"Szczerbinski","year":"2023","journal-title":"Lancet Diabetes Endocrinol"},{"key":"R15-20260617","doi-asserted-by":"crossref","first-page":"e1171","DOI":"10.1002\/prp2.1171","article-title":"Epigenetics in obesity: Mechanisms and advances in therapies based on natural products","volume":"12","author":"Chen","year":"2024","journal-title":"Pharmacol Res Perspect"},{"key":"R16-20260617","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1038\/s41588-021-00945-5","article-title":"An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci","volume":"53","author":"Mountjoy","year":"2021","journal-title":"Nat Genet"},{"key":"R17-20260617","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/j.ajhg.2022.08.005","article-title":"Addressing underrepresentation in genomics research through community engagement","volume":"109","author":"Lemke","year":"2022","journal-title":"Am J Hum Genet"}],"container-title":["International Journal of Applied & Basic Medical 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