RGD Reference Report - Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Quebec Family Study. - Rat Genome Database

RGD Reference Report - Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Quebec Family Study. - Rat Genome Database

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Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Quebec Family Study.
Authors:	Chagnon, YC Chen, WJ Perusse, L Chagnon, M Nadeau, A Wilkison, WO Bouchard, C
Citation:	Chagnon YC, etal., Mol Med. 1997 Oct;3(10):663-73.
RGD ID:	1626222
Pubmed:	PMID:9392003 (View Abstract at PubMed)
PMCID:	PMC2230227 (View Article at PubMed Central)
BACKGROUND: The agouti yellow mouse shows adult onset of moderate obesity and diabetes. A depressed basal lipolytic rate in adipocytes or a decreased adrenergic tone arising from antagonizing alpha-melanocyte-stimulating hormone (MSH) activation of melanocortin receptors (MCR) could be at the origin of the obesity phenotype. MATERIAL AND METHODS: MCR 4 and 5 (MC4R, MC5R) genes were studied in the Quebec Family Study. Sequence variations were detected by Southern blot probing of restricted genomic DNA, and mRNA tissue expression was detected by RT-PCR. Subjects with a wide range of weight were used for single-point sib-pair linkage studies (maximum of 289 sibships from 124 nuclear families). Analysis of variance across genotypes in unrelated males (n = 143) and females (n = 156) was also undertaken. Body mass index (BMI), sum of six skin-folds (SF6), fat mass (FM), percent body fat (%FAT), respiratory quotient (RQ), resting metabolic rate (RMR), fasting glucose and insulin, and glucose and insulin area during an oral glucose tolerance test were analyzed. RESULTS: MC4R showed polymorphism with NcoI, and MC5R, with PstI and PvuII, with a heterozygosity of 0.38, 0.10, and 0.20, respectively. Linkages were observed between MC5R and BMI (p = 0.001), SF6 (p = 0.005), FM (p = 0.001), and RMR (p = 0.002), whereas associations were observed in females between MC5R and BMI (p = 0.003), and between MC4R and FM (p = 0.002) and %FAT (p = 0.004). After correction for multiple tests, these p values are lowered by one tenth. MC4R and MC5R mRNAs have been detected in brain, adipose tissue, and skeletal muscle. CONCLUSIONS: MC4R and MC5R exhibit evidence of linkage or association with obesity phenotypes, but this evidence is strongest for MC5R.

Phenotype Annotations Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Increased adipose tissue		IAGP		1626222; 1626222		RGD
Increased body fat percentage		IAGP		1626222		RGD
Increased body mass index		IAGP		1626222		RGD

Objects Annotated

Genes (Homo sapiens)

MC4R (melanocortin 4 receptor)

MC5R (melanocortin 5 receptor)

Objects referenced in this article

Gene	Mc4r	melanocortin 4 receptor	Mus musculus
Gene	Mc5r	melanocortin 5 receptor	Mus musculus
Gene	Mc4r	melanocortin 4 receptor	Rattus norvegicus
Gene	Mc5r	melanocortin 5 receptor	Rattus norvegicus

Additional Information