Association of anorexia nervosa with the high activity allele of the COMT gene: a family-based study in Israeli patients

Anorexia nervosa (AN) is a common, severe and disabling psychiatric disorde r, characterized by profound weight loss and body image disturbance.(1) Fam ily and twin studies indicate a significant genetic contribution(2,3) and p harmacological data suggest possible dysfunction of the serotonergic(4,5) a nd dopaminergic(6-9) pathways. Catechol-O-methyltransferase (COMT) is a can didate gene for mediating susceptibility to AN since it is involved in the dopamine catabolism(10) and because its functional polymorphism (Val/Met 15 8) determines high (H) and low (L) enzymatic activity alleles.(11) Fifty-on e Israeli AN patients and their parents were genotyped with the COMT polymo rphism. Using the haplotype relative risk (HRR) method it was found that th e frequency of the H allele among alleles transmitted to AN patients from t heir parents was significantly higher than in those not transmitted (68% vs 51% chi (2) = 5.20 df = 1, P = 0.023, odds ratio: 2.01). Transmission dise quilibrium test (TDT) revealed that out of 49 heterozygote parents the H al lele was transmitted to AN patients 33 times while the L allele was transmi tted only 16 (McNemar's chi (2) = 5.90, df = 1, P = 0.015). Our study sugge sts that the COMT gene is associated with genetic susceptibility to AN, and that individuals homozygous for the high activity allele (HH) have a two-f old increased risk for development of the disorder.