1. ¹Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA
2. ²Department of Medical Biology, School of Medicine, Afyonkarahisar Kocatepe University, Afyonkarahisar, Turkey

Correspondence: Dr MA Sözen, Department of Medical Biology, School of Medicine, Afyonkarahisar Kocatepe University, Ali Çetinkaya Kampüsü, Afyonkarahisar-zmir yolu 6.km, Afyonkarahisar 03200, Turkey. E-mail: masozen@hotmail.com

Received 18 August 2006; Revised 12 October 2006; Accepted 18 October 2006; Published online 20 December 2006.

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.