GENETIC-POLYMORPHISM OF CATECHOL-O-METHYLTRANSFERASE (COMT) - CORRELATION OF GENOTYPE WITH INDIVIDUAL VARIATION OF S-COMT ACTIVITY AND COMPARISON OF THE ALLELE FREQUENCIES IN THE NORMAL POPULATION AND PARKINSONIAN-PATIENTS IN FINLAND

The catechol-O-methyltransferase (COMT) gene occurs as two polymorphic alleles, which code for a high activity thermostable and low activity thermolabile form of the enzyme. We devised a fast solid-phase minise quencing assay for genotyping the COMT gene at nucleotide position 544 encoding amino acid residue 158. The method was applied to correlate the genotype of the COMT gene with the biological activity of the COMT enzyme. In red blood cells from individuals homozygous for G at nucle otide position 544 coding for Val-158, the activity of COMT ranged fro m 0.55-1.03 pmolmin(-1)mg(-1) protein, and in individuals homozygous f or A at position 544 coding for Met-158, the activity ranged from 0.21 -0.43 pmolmin(-1)mg(-1). Heterozygotes showed intermediate activities of 0.20-0.88 pmolmin(-1)mg(-1). The thermostability (heated/unheated) at 48 degrees C of the high activity form was shown to be about two-fo ld compared to that of the low activity form of the enzyme. By analysi ng 76 individual samples and three pooled samples representing altoget her 3140 individuals using the solid-phase minisequencing method, the two COMT alleles were shown to be equally distributed in the Finnish p opulation. No statistically significant difference in the frequencies of the COMT alleles was found when comparing the normal population wit h a sample of 158 Finnish patients with Parkinson's disease.