Catechol-O-methyltransferase Vall58Met 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 (Metl 58; COMT^L) is less frequent with about 7% being homozygous. Using a PCR based genotyping assay, we report that the Metl 58 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 22q 11, we have analysed the COMT Vail 58Met polymorphism as a candidate susceptibility factor for bipolar affective disorder. We report an association between bipolar affective disorder and the Metl 58 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-0- methyltransferase is a risk factor for bipolar affective disorder in Chinese populations or is in linkage disequilibrium with a nearby susceptibility gene or polymorphism.