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A rare mutation in AgRP, +79G>A, affects promoter activity

European Journal of Clinical Nutrition volume 61, pages 809–812 (2007)Cite this article

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.

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Acknowledgements

This work was supported by the National Institutes of Diabetes and Digestive and Kidney Diseases (DK62156 to GA). We thank Drs Claude Bouchard and Tuomo Rankinen for making available DNA samples to screen for the presence of mutations in AgRP. We also thank Dr Donna Ryan for facilitating the sample collection of the Pennington Biomedical Research Center cohort.

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Authors and Affiliations

  1. Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA

    M A Sözen, L H M de Jonge, F Greenway, E Ravussin, S R Smith & G Argyropoulos

  2. Department of Medical Biology, School of Medicine, Afyonkarahisar Kocatepe University, Afyonkarahisar, Turkey

    M A Sözen

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  1. M A Sözen
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  2. L H M de Jonge
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  3. F Greenway
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  4. E Ravussin
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  5. S R Smith
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  6. G Argyropoulos
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Corresponding author

Correspondence to M A Sözen.

Additional information

Guarantor: G Argyropoulos.

Contributors: MAS discovered the +79G>A mutation and performed the functional studies in cell culture. LHMdJ assisted with the data analysis for the resting metabolic rate. FG, ER and SRS made available samples and resting metabolic rate data from existing cohorts. GA conceived and supervised the project, and wrote the manuscript.

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Sözen, M., de Jonge, L., Greenway, F. et al. A rare mutation in AgRP, +79G>A, affects promoter activity. Eur J Clin Nutr 61, 809–812 (2007). https://doi.org/10.1038/sj.ejcn.1602585

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