Candidate gene polymorphisms in eating disorders

Anorexia nervosa and bulimia nervosa are complex disorders characterized by disordered eating behaviour. Attitudes towards weight and shape as well as the perception of body shape are disturbed. A substantial genetic influence on these disorders has been suggested by formal genetic studies. Obsessive-compulsive behaviour, perfectionism and anxious personality traits seem to occur premorbidly in several patients. Disturbances of neurotransmitter, neuropeptide and neuroendocrine systems have been reported in acutely ill and followed-up patients. Hence, these systems might be involved in the etiology of these eating disorders. Genetic studies on candidate genes have mainly focussed on the serotonergic system and on genes involved in body weight regulation. Up to now, polymorphisms and variations in various genes (e.g. genes for 5-HT receptors. leptin gene, melanocortin MC, receptor gene) have been assessed for association and transmission disequilibrium pertaining to anorexia nervosa and/or bulimia nervosa. Most of the studies yielded negative results. Four studies of a polymorphism (-1438 G/A) within the promoter of the 5-HT2A gene (5-HT2A) revealed an association of the A-allele to anorexia nervosa. However, three studies could not confirm this result. Furthermore, a meta-analysis did not support the positive association. Currently, combined efforts within the European Union will answer the question of whether or not the A-allele is involved in the predisposition to anorexia nervosa. A transmission disequilibrium test is being performed in about 300 trios consisting of a patient with anorexia nervosa and both parents. As candidate gene approaches did not unequivocally identify susceptibility genes (alleles) for anorexia nervosa or bulimia nervosa, systematic model-free genome-wide screenings should also be performed in order to identify currently unknown genes involved in eating disorders. This kind of approach has already been initiated for anorexia nervosa. Genetic research on eating disorders will hopefully lead to new pharmacological treatment strategies. (C) 2000 Elsevier Science B.V. All rights reserved.