title: Catechol-O-methyltransferase Val158Met polymorphism: frequency analysis in Han Chinese subjects and allelic association of the low activity allele with bipolar affective disorder.
abstract: 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.
authors.affiliation: Institute of Psychiatry, Section of Molecular Genetics, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Vallada
authors.forename: D
authors.initials: D
authors.lastname: Curtis
authors.forename: M
authors.initials: M
authors.lastname: Arranz
authors.forename: K
authors.initials: K
authors.lastname: Xu
authors.forename: G
authors.initials: G
authors.lastname: Cai
authors.forename: H
authors.initials: H
authors.lastname: Deng
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: R
authors.initials: R
authors.lastname: Murray
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: D A
authors.initials: DA
authors.lastname: Collier
mesh_terms: 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*
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine