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 disorder, characterized by profound weight loss and body image disturbance. Family and twin studies indicate a significant genetic contribution and pharmacological data suggest possible dysfunction of the serotonergic and dopaminergic pathways. Catechol-O-methyltransferase (COMT) is a candidate gene for mediating susceptibility to AN since it is involved in the dopamine catabolism and because its functional polymorphism (Val/Met 158) determines high (H) and low (L) enzymatic activity alleles. Fifty-one Israeli AN patients and their parents were genotyped with the COMT polymorphism. Using the haplotype relative risk (HRR) method it was found that the frequency of the H allele among alleles transmitted to AN patients from their 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 disequilibrium test (TDT) revealed that out of 49 heterozygote parents the H allele was transmitted to AN patients 33 times while the L allele was transmitted only 16 (McNemar's chi(2) = 5.90, df = 1, P = 0.015). Our study suggests that the COMT gene is associated with genetic susceptibility to AN, and that individuals homozygous for the high activity allele (HH) have a two-fold increased risk for development of the disorder.
Frisch
A
A
Felsenstein Medical Research Center, Petah Tikva, 49 100 Israel. afrisch@post.tau.ac.il
Laufer
N
N
Danziger
Y
Y
Michaelovsky
E
E
Leor
S
S
Carel
C
C
Stein
D
D
Fenig
S
S
Mimouni
M
M
Apter
A
A
Weizman
A
A
D000293:Adolescent; D000483:Alleles; D000856:Anorexia Nervosa / Q000453:epidemiology / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007557:Israel; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic; D012307:Risk Factors
D002394:Catechol O-Methyltransferase