Catechol-O-methyltransferase Val158Met polymorphism: frequency analysis in Han Chinese subjects and allelic association of the low activity allele with bipolar affective disorder.
Catechol-O-methyltransferase catalyses the O-methylation of biologically active or toxic catechols and is a major component of the metabolism of drugs and neurotransmitters such as L-dopa, noradrenaline, adrenaline, and dopamine. Human catechol-O-methyltransferase activity is an autosomal partially dominant trait and is strongly associated with a valine to methionine substitution at codon 158 of the protein. About 25% of Caucasians have low activity, 50% intermediate activity and 25% high activity as determined by either phenotypic or genotypic measurement. In black populations, the low activity allele (Met158; COMTL) is less frequent with about 7% being homozygous. Using a PCR based genotyping assay, we report that the Met158 allele is also less frequent in normal Han Chinese subjects with about 3% of the population being homozygous. Because of its role in catecholamine metabolism and several lines of evidence pointing to a locus for psychosis near the COMT gene on chromosome 22q11, we have analysed the COMT Val158Met polymorphism as a candidate susceptibility factor for bipolar affective disorder. We report an association between bipolar affective disorder and the Met158 allele (p = 0.004) and genotype (p = 0.01) in 93 affected Chinese subjects and 98 controls. We hypothesize that either the low activity allele of catechol-O-methyltransferase is a risk factor for bipolar affective disorder in Chinese populations or is in linkage disequilibrium with a nearby susceptibility gene or polymorphism.
Li
T
T
Institute of Psychiatry, Section of Molecular Genetics, London, UK.
Vallada
H
H
Curtis
D
D
Arranz
M
M
Xu
K
K
Cai
G
G
Deng
H
H
Liu
J
J
Murray
R
R
Liu
X
X
Collier
D A
DA
D001714:Bipolar Disorder / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002681:China / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D014633:Valine / Q000235:genetics*
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine