Inheritance of Low Immunoreactive Human Plasma Dopamine-β-Hydroxylase

A C T Inheritance plays an important role in the determination of human plasma dopamine-,8hydroxylase (DBH) enzymatic activity. It has been demonstrated that an allele (d) for very low enzymatic plasma DBH is inherited as an autosomal recessive trait. A radioimmunoassay for human DBH was de- veloped to test the hypothesis that the presence of this allele results in a decrease in plasma DBH protein lev- els. The mean immunoreactive DBH (IDBH) in blood from a randomly selected population of adolescents was 82438 ng/ml (meanSEM, n = 134). The correla- tion coefficient of enzymatic DBH with IDBH for this group of 134 adolescents was 0.84 (P < 0.001). Ofthese subjects, 3.7% had values of <100 ng/ml and appeared to compose a separate subgroup analogous to the 3-4% of the population that is homozygous for the allele for low enzymatic activity. There was a significant sibling- sibling correlation of IDBH values in the 14 sibling pairs included among the 134 subjects studied (r = 0.60, P < 0.025). IDBH was also measured in blood from 56 subjects homozygous (dd) for the allele for low enzy- matic DBH (enzymatic activity < 50 U/ml) and in blood of 80 first-degree relatives of homozygous probands. All but two dd subjects had IDBH levels of <100 ng/ml. Results of family studies were compatible with the autosomal recessive inheritance of an allele for IDBH levels of less than 100 ng/ml which segregates with the allele for very low enzymatic activity. Average IDBH in blood of 37 obligate heterozygotes as deter- mined by family studies (Dd) was 59953 ng/ml (mean +4SEM), significantly lower than the IDBH values found in a randomly selected population (P < 0.005). These results are compatible with the conclusion that Dr. Weinshilboum is an Established Investigator of the American Heart Association.