title: COMT Val158Met variant and functional haplotypes associated with childhood ADHD history in women with bulimia nervosa.
abstract: Up to one third of patients with bulimia nervosa (BN) report a history of ADHD symptoms, and both disorders may also be associated with dopaminergic abnormalities. COMT gene, coding for an enzyme responsible for the degradation of dopamine, may play a part in the etiology of ADHD and BN. This study aimed to (1) examine if certain variants of the COMT genetic markers (rs6269, rs4633, rs4818 and rs4680) are more common in BN versus controls; (2) assess transmission of COMT alleles in BN families; and (3) explore the role of COMT genotypes and haplotypes in bulimic women with childhood ADHD history. 72 BN probands and unaffected relatives were genotyped for COMT rs4680 (Val158Met) and three adjacent markers. The remaining 165 probands were matched with nonpsychiatric controls. We also investigated if COMT variants and haplotypes were associated with childhood ADHD history in a subgroup of 86 BN probands who completed the Wender Utah Rating Scale (WURS). Our results showed that cases and controls did not differ in COMT allele and haplotype frequencies. In contrast, specific alleles of all four COMT markers and the medium-activity haplotype were preferentially transmitted to the offspring with BN. COMT Val158 allele was overrepresented and the medium-activity haplotype was underrepresented in BN with childhood ADHD history (p=0.010). These findings suggest a possible role for COMT variants and related haplotypes in BN and its subphenotypes. If replicated, these preliminary findings may have implications for the prevention and treatment of BN that emerges in the context of childhood ADHD.
authors.affiliation: Institute of Medical Science, University of Toronto, 7213 Medical Science Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8. zeynep.yilmaz@utoronto.ca
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Yilmaz
authors.forename: Allan S
authors.initials: AS
authors.lastname: Kaplan
authors.forename: Clement C
authors.initials: CC
authors.lastname: Zai
authors.forename: Robert D
authors.initials: RD
authors.lastname: Levitan
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics* / Q000523:psychology; D052018:Bulimia Nervosa / Q000150:complications / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002395:Catecholamines / Q000502:physiology; D002648:Child; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005190:Family; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D055815:Young Adult
chemical_list: D002395:Catecholamines; D005819:Genetic Markers; D002394:Catechol O-Methyltransferase