Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: differences between restricting and binging/purging subtypes.

Anorexia nervosa (AN) is a severe and disabling psychiatric disorder, characterized by profound weight loss and body image disturbance. Family and twin studies indicate a significant genetic contribution to this disorder although no genetic mutation has yet been identified. The endocannabinoid system has recently been implicated in many physiological functions including appetite regulation. We, therefore, undertook a family based study to test the hypothesis whether a polymorphism of the CNR1 gene, which encodes human CB1 receptor, a subclass of the central cannabinoid receptor, contributes to the susceptibility to AN. Fifty two families (parents with one or two affected siblings) were genotyped for the (AAT) trinucleotide repeat of CNR1 gene. Using the haplotype relative risk (HRR) method, the distribution of alleles transmitted to the patients was not found to be significantly different from the non-transmitted parental alleles. However, upon dividing the samples to restricting and binging/purging subtypes of AN, the extended transmission disequilibrium test (ETDT) revealed that there is preferential transmission of different alleles in each of the subtypes. The 14 repeat allele was preferentially transmitted in the binging/purging AN group (P = 0.05) but not in the restricting AN group, whereas the 13 repeat allele was preferentially transmitted in the restricting AN group (almost significant, P = 0.07) but not in the binging/purging AN group. Our study suggests that restricting AN and binging/purging AN may be associated with different alleles of the CNR1 gene.