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 biological ly active or toxic catechols and is a major component of the metabolis m of drugs and neurotransmitters such as I.-dopa, noradrenaline, adren aline, 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 2 5% of Caucasians have low activity, 50% intermediate activity and 25% high activity as determined by either phenotypic or genotypic measurem ent, fm black populations, the low activity allele (Met158; COMTL) is less frequent with about 7% being homozygous. Using a PCR based genoty ping assay, we report that the Met158 allele is also less frequent in normal Han Chinese subjects with about 3% of the population being homo zygous. Because of its role in catecholamine metabolism and several Li nes of evidence pointing to a locus for psychosis near the COMT gene o n chromosome 22q11, we have analysed the COMTVal158Met polymorphism as a candidate susceptibility factor for bipolar affective disorder, We report an association between bipolar affective disorder and the MET15 8 allele (p = 0.004) and genotype (p = 0.01) in 93 affected Chinese su bjects and 98 controls. We hypothesize that either the low activity al lele of catechol-O-methyltransferase is a risk factor for bipolar affe ctive disorder in Chinese populations or is in linkage disequilibrium with a nearby susceptibility gene or polymorphism.