Low activity allele of catechol-O-methyltransferase gene associated with rapid cycling bipolar disorder

• Published in: Molecular psychiatry Vol. 3; no. 4; pp. 342 - 345
• Main Authors: KIROV, G, MURPHY, K. C, CRADDOCK, N, ARRANZ, M. J, JONES, I, MCCANDLES, F, KUNUGI, H, MURRAY, R. M, MCGUFFIN, P, COLLIER, D. A, OWEN, M. J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.07.1998
• Subjects: Adult and adolescent clinical studies; Alleles; Amino Acid Substitution; Amino acids; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - enzymology; Bipolar Disorder - epidemiology; Bipolar Disorder - genetics; Bipolar Disorder - psychology; Bipolar disorders; Catechol; Catechol O-methyltransferase; Catechol O-Methyltransferase - genetics; Catecholamines; Female; Gene polymorphism; Humans; Hypotheses; Male; Medical sciences; Methionine; Methyltransferase; Middle Aged; Mood disorders; Point Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Population genetics; Population studies; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Risk Assessment; United Kingdom; Whites; United Kingdom; Mood disorder; Human; Allele; Methyltransferases; Enzyme; Transferases; Risk factor; Clinical form; Genetics; Bipolar disorder; Catechol O-methyltransferase; Polymorphism
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4000385

Catechol-O-methyltransferase (COMT) plays a major role in the breakdown of catecholamines. An amino acid polymorphism (val-108-met) determines high and low activity of the enzyme. A recent study in a small sample of patients with velo-cardio-facial syndrome who had bipolar affective disorder suggested that the Met (low activity) COMT allele might be associated with rapid-cycling in this population. We therefore tested the hypothesis that the Met allele might be associated with rapid cycling bipolar disorder in the wider population. We studied a sample of British Caucasian DSM-IV bipolar patients, of whom 55 met criteria for rapid cycling at some time during the illness and 110 met stringent criteria for a definite non-rapid cycling course. The COMT genotype was determined using a PCR assay. The low activity allele was more frequent in the group of rapid cyclers: 0.55 vs 0.42 (one-tailed chi 2 = 5.12, d.f. = 1, P = 0.012), and bearers of low activity alleles showed a dose-dependent increased risk of lifetime occurrence of rapid cycling: chi 2 test of linear association = 4.84, d.f. = 1, P = 0.014. Our data support the hypothesis that variation in the COMT gene modifies the course of bipolar disorder.