RGD Reference Report - A polymorphism in the human agouti-related protein is associated with late-onset obesity. - Rat Genome Database

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A polymorphism in the human agouti-related protein is associated with late-onset obesity.

Authors: Argyropoulos, G  Rankinen, T  Neufeld, DR  Rice, T  Province, MA  Leon, AS  Skinner, JS  Wilmore, JH  Rao, DC  Bouchard, C 
Citation: Argyropoulos G, etal., J Clin Endocrinol Metab. 2002 Sep;87(9):4198-202.
RGD ID: 1625232
Pubmed: PMID:12213871   (View Abstract at PubMed)
DOI: DOI:10.1210/jc.2002-011834   (Journal Full-text)

The mouse agouti-related protein (AGRP) is a powerful appetite effector that results in hyperphagia and the development of obesity when administered intracerebroventricularly or when overexpressed in transgenic mice. Animal studies have also shown that exogenous administration of AGRP predisposes toward hedonic intake of high fat and high sucrose diets. The human ortholog (hAGRP) maps on chromosome 16q22 and has similar physiological properties, as tested in animal models. A polymorphism was identified in the third exon of hAGRP, c.199G-->A, that resulted in a nonconservative amino acid substitution, Ala(67)Thr. Computational analysis of the protein showed significant differences in the coils of the two polymorphic isoforms of the protein. Human studies showed no genotype effects in individuals with a mean age of 25 yr. However, the G/G genotype was significantly associated with fatness and abdominal adiposity in the parental population with a mean age of 53 yr. The c.199G-->A polymorphism in hAGRP could, therefore, play a role in the development of human obesity in an age-dependent fashion.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
obesity  IAGP 1625232DNA:polymorphism:exon:c.199G>A and pAla67Thr (human)RGD 
obesity  ISOAGRP (Homo sapiens)1625232; 1625232DNA:polymorphism:exon:c.199G>A and pAla67Thr (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Increased body weight  IAGP 1625232DNA:polymorphism:exon:c.199G>A and pAla67ThrRGD 
Objects Annotated

Genes (Rattus norvegicus)
Agrp  (agouti related neuropeptide)

Genes (Mus musculus)
Agrp  (agouti related neuropeptide)

Genes (Homo sapiens)
AGRP  (agouti related neuropeptide)


Additional Information