Ethnic differences in erythrocyte catechol-O-methyltransferase activity in black and white Americans

Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catecholamine and catechol drugs such as levodopa and methyldopa. Human COMT activity is inherited as an autosomal co-dominant trait; approximately 25% of white individuals have low activity consistent with homozygosity for a low activity allele, about 50% have intermediate activity (i.e., heterozygous genotype) and 25% have high activity. COMT activity has not been characterized in African-Americans or other black populations. To investigate potential ethnic and gender differences in COMT, we measured erythrocyte COMT activity in 195 unrelated black and 202 unrelated white healthy individuals living in the Southeast United States. Overall, the black population had significantly higher COMT activity than the white population (median 15.7 vs. 11.4 U/ml of packed red blood cell volume; P < .001). Maximum likelihood estimation of COMT activity distribution identified significant ethnic differences, with high activity in 23% of whites and 55% of blacks, intermediate activity in 50% of whites and 38% of blacks and low activity in 27% of whites and 7% of blacks. No greater differences in COMT activity were observed in either ethnic group. We conclude that red blood cell COMT activity is significantly higher in black subjects than white subjects. Hardy-Weinberg estimates indicate that this ethnic difference is due to a higher frequency of high activity COMT alleles in blacks vs. whites (0.74 vs. 0.48).