Low activity allele of catechol-O-methyltransferase gene associated with rapid cycling bipolar disorder.
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.
Neuropsychiatric Genetics Unit, University of Wales College of Medicine, Heath Park, Cardiff, UK. kirov@cardiff.ac.uk
G
G
Kirov
K C
KC
Murphy
M J
MJ
Arranz
I
I
Jones
F
F
McCandles
H
H
Kunugi
R M
RM
Murray
P
P
McGuffin
D A
DA
Collier
M J
MJ
Owen
N
N
Craddock
D000483:Alleles; D019943:Amino Acid Substitution; D001714:Bipolar Disorder / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D006113:United Kingdom; D044465:White People
D002394:Catechol O-Methyltransferase