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

George Argyropoulos, Tuomo Rankinen, Doni R. Neufeld, Treva Rice, Michael A. Province, Arthur S. Leon, James S. Skinner, Jack H. Wilmore, D. C. Rao, Claude Bouchard

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

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, Ala67Thr. 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.

Original languageEnglish
Pages (from-to)4198-4202
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number9
DOIs
StatePublished - Sep 2002

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