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  • Original Research Article
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Association between an agouti-related protein gene polymorphism and anorexia nervosa

Abstract

Anorexia nervosa (AN) is a life threatening disorder affecting mostly adolescent women. It is a dramatic psychiatric syndrome accompanied by severe weight loss, hyperactivity and neuroendocrine changes (reviewed in Refs 1 and 2). Several studies have shown a strong genetic component in AN (reviewed in Ref 3). Recent advances in unraveling the mechanisms of weight control4 point to a crucial role of the melanocortin-4 receptor (MC4-r) system in regulating body weight. The orexigenic neuropeptide agouti-related protein (AGRP), a MC4-r antagonist, plays a crucial role in maintaining body weight, by inducing food intake. The sequence of the coding region of the human AGRP gene (AGRP) was determined and the AGRP of 100 patients with AN was screened for variations. Three single nucleotide polymorphisms (SNPs) were identified and screened in a further 45 patients and 244 controls. Two alleles were in complete linkage disequilibrium and were significantly enriched in anorectic patients (11%; P = 0.015) compared to controls (4.5%). These data indicate that variations of AGRP are associated with susceptibility for AN. This is possibly caused by defective suppression of the MC4-r by the variant AGRP, leading to a decreased feeding signal, increasing the risk of developing AN. These results implicate that antagonism of the MC4-r might be considered as pharmacotherapy for patients with AN.

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Acknowledgements

We thank J Hop for her contribution in obtaining the Dutch AN samples. We thank the families for their participation. This study was supported by the European Community (Framework V ‘Factors in healthy eating’) and the Deutsche Forschungsgemeinschaft.

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Correspondence to R A H Adan.

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Vink, T., Hinney, A., van Elburg, A. et al. Association between an agouti-related protein gene polymorphism and anorexia nervosa. Mol Psychiatry 6, 325–328 (2001). https://doi.org/10.1038/sj.mp.4000854

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