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.
Kirov
G
G
Neuropsychiatric Genetics Unit, University of Wales College of Medicine, Heath Park, Cardiff, UK. kirov@cardiff.ac.uk
Murphy
K C
KC
Arranz
M J
MJ
Jones
I
I
McCandles
F
F
Kunugi
H
H
Murray
R M
RM
McGuffin
P
P
Collier
D A
DA
Owen
M J
MJ
Craddock
N
N
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