title: A rare mutation in AgRP, +79G>A, affects promoter activity.
abstract: The agouti-related protein is a powerful orexigenic peptide. A rare mutation, +79G>A, was identified in its minimal promoter in two white carriers. Comparison of the 45-year-old male proband, who was also a carrier of the common Ala67Thr polymorphism, with an age- and weight-matching wild-type population showed marginal differences for resting metabolic rate (RMR) and body mass index. The second carrier however was an obese 57-year-old female with reduced RMR. Functional analysis in hypothalamus- and periphery-derived cell lines showed reduced promoter activity for the +79A allele in the adrenocortical cells only, suggesting that it could affect the peripheral expression levels of AgRP. The +79G>A mutation could predispose to body weight gain (as suggested by the phenotype of the second carrier), but it could only affect the proband at an older age as he may be protected by the Ala67Thr polymorphism that is associated with resistance to late-onset fatness.
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA. masozen@hotmail.com
authors.forename: M A
authors.initials: MA
authors.lastname: Sözen
authors.forename: L H M
authors.initials: LH
authors.lastname: de Jonge
authors.forename: F
authors.initials: F
authors.lastname: Greenway
authors.forename: E
authors.initials: E
authors.lastname: Ravussin
authors.forename: S R
authors.initials: SR
authors.lastname: Smith
authors.forename: G
authors.initials: G
authors.lastname: Argyropoulos
mesh_terms: D054369:Agouti-Related Protein; D001481:Basal Metabolism / Q000235:genetics* / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013851:Thinness / Q000235:genetics / Q000378:metabolism
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins