Screening of candidate genes in patients with anorexia nervosa

Objective: Family and twin studies suggest a genetic contribution to anorexia nervosa (AN). Psychopathological features and extremely low body weight are inseparable in AN, so that AN might be considered as an extreme weight condition. The prevalence of this eating disorder is considerably higher in females. The manifestation for AN is predominantly in puberty. A candidate gene approach needs to consider these clinical observations. The genes we analyzed can accordingly be categorized as follows: genes relevant in (a) weight regulation (leptin gene; neuropeptide Y [NPY] Y5 receptor gene); (b) hormonal changes during female puberty (estrogen beta receptor gene); and (c) neurotransmitter receptors (serotonergic system: 5-HT_1Dβ-, 5-HT_2A-, 5-HT_2C-, and 5-HT₇ receptor genes and a promoter polymorphism in the 5-HT transporter gene; dopaminergic system: DRD4 gene). Methods: We screened for mutations by PCR-RFLP, PCR-SSP, SSCP, and temperature gradient gel electrophoresis, respectively, in up to 143 patients with AN, 154 underweight students, and 366 extremely obese children and adolescents to perform association studies. Additionally, up to 55 trios comprising a patient with AN and both parents were genotyped in order to perform transmission disequilibrium tests. Results: Some novel mutations that were not relevant for AN were detected in the leptin gene and in the NPY Y5 receptor gene. None of the association or transmisssion disequilibrium tests rendered P values < 0.1. Conclusion: Variations in the analyzed candidate genes are not of importance for the development of AN in our study group.