ArticleHuman molecular genetics2009
Association of functionally significant Melanocortin-4 but not Melanocortin-3 receptor mutations with severe adult obesity in a large North American case-control study.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 128 citations in OpenAlex.
- Trial
- Cross-species studies implicate the melanocortin 3 receptor more strongly in the control of pubertal development than energy balance.Molecular metabolism · 2026Article
- MC4R Variants Modulate α-MSH and Setmelanotide Induced Cellular Signaling at Multiple Levels.The Journal of clinical endocrinology and metabolism · 2024Article
- Serum levels of Vanin-2 increase with obesity in relation to inflammation of adipose tissue and may be a predictor of bariatric surgery outcomes.Frontiers in nutrition · 2023Article
- Lipocalin 2 - mutation screen and serum levels in patients with anorexia nervosa or obesity and in lean individuals.Frontiers in endocrinology · 2023Article
- The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects.Scientific reports · 2021Article
- Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations.International journal of obesity (2005) · 2021 · on this mapArticle
- Biomarkers for Lifetime Caries-Free Status.Journal of personalized medicine · 2020Article
- The role of polygenic susceptibility to obesity among carriers of pathogenic mutations in MC4R in the UK Biobank population.PLoS medicine · 2020Article
- The Effect Sizes ofGenes · 2020Article
- Identification of a Rare and Potential PathogenicFrontiers in genetics · 2020Article
- Phenotypic and genetic analysis of an adult cohort with extreme obesity.International journal of obesity (2005) · 2019Article
- Associations of the melanocortin 3 receptor C17A + G241A haplotype with body composition and inflammation in African-American adults.Annals of human genetics · 2019Article
- Characterization of Rare Variants in MC4R in African American and Latino Children With Severe Early-Onset Obesity.The Journal of clinical endocrinology and metabolism · 2019Article
- Article
- Heterozygous versus homozygous phenotype caused by the same MC4R mutation: novel mutation affecting a large consanguineous kindred.BMC medical genetics · 2018Article
- Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.Nature genetics · 2018Article
- Polymorphisms in Genes Involved in the Leptin-Melanocortin Pathway are Associated with Obesity-Related Cardiometabolic Alterations in a Southern Chilean Population.Molecular diagnosis & therapy · 2018Article
- Polymorphisms and mutations in the melanocortin-3 receptor and their relation to human obesity.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Prevalence and phenotypic characterization of MC4R variants in a large pediatric cohort.International journal of obesity (2005) · 2017Article
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Authors and funding
12 authors at 7 institutions in 4 countries.
Funding
Abstract
Functionally significant heterozygous mutations in the Melanocortin-4 receptor (MC4R) have been implicated in 2.5% of early onset obesity cases in European cohorts. The role of mutations in this gene in severely obese adults, particularly in smaller North American patient cohorts, has been less convincing. More recently, it has been proposed that mutations in a phylogenetically and physiologically related receptor, the Melanocortin-3 receptor (MC3R), could also be a cause of severe human obesity. The objectives of this study were to determine if mutations impairing the function of MC4R or MC3R were associated with severe obesity in North American adults. We studied MC4R and MC3R mutations detected in a total of 1821 adults (889 severely obese and 932 lean controls) from two cohorts. We systematically and comparatively evaluated the functional consequences of all mutations found in both MC4R and MC3R. The total prevalence of rare MC4R variants in severely obese North American adults was 2.25% (CI(95%): 1.44-3.47) compared with 0.64% (CI(95%): 0.26-1.43) in lean controls (P < 0.005). After classification of functional consequence, the prevalence of MC4R mutations with functional alterations was significantly greater when compared with controls (P < 0.005). In contrast, the prevalence of rare MC3R variants was not significantly increased in severely obese adults [0.67% (CI(95%): 0.27-1.50) versus 0.32% (CI(95%): 0.06-0.99)] (P = 0.332). Our results confirm that mutations in MC4R are a significant cause of severe obesity, extending this finding to North American adults. However, our data suggest that MC3R mutations are not associated with severe obesity in this population.
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