TY - JOUR
T1 - Association of anorexia nervosa with the high activity allele of the COMT gene
T2 - A family-based study in Israeli patients
AU - Frisch, A.
AU - Laufer, N.
AU - Danziger, Y.
AU - Michaelovsky, E.
AU - Leor, S.
AU - Carel, C.
AU - Stein, D.
AU - Fenig, S.
AU - Mimouni, M.
AU - Apter, A.
AU - Weizman, A.
N1 - Funding Information:
This study was supported by grants (42-97) from the National Institute for Psychobiology in Israel and (610-212.02) from the German–Israeli Foundation for scientific research and development (GIF).
PY - 2001
Y1 - 2001
N2 - 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% χ2 = 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 χ2 = 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.
AB - 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% χ2 = 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 χ2 = 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.
KW - Catechol-O-methyltransferase (COMT)
KW - Eating disorders
KW - Haplotype relative risk (HRR)
KW - Polymorphism
KW - Transmission disequilibrium test (TDT)
UR - http://www.scopus.com/inward/record.url?scp=17744363444&partnerID=8YFLogxK
U2 - 10.1038/sj.mp.4000830
DO - 10.1038/sj.mp.4000830
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AN - SCOPUS:17744363444
SN - 1359-4184
VL - 6
SP - 243
EP - 245
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 2
ER -