Genetics of red cell COMT activity: Analysis of thermal stability and family data

R. S. Spielman, R. M. Weinshilboum

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100 Scopus citations


Previous studies have shown that the activity of human red cell catechol-O-methyltransferase (RBC COMT) is significantly correlated in sibs, that the population distribution is bimodal, and that RBC COMT from individuals with low activity is more thermolabile than that from individuals with high activity. These observations and additional data from family studies are consistent with the hypothesis that RBC COMT activity is controlled by two alleles at an autosomal locus [Weinshilboum and Raymond, 1977], giving rise to genotypes with different but overlapping activity distributions. In the present study, this hypothesis has been explored with various types of analyses. Given the assumption of Hardy-Weinberg genotype frequencies, we find that the population distribution of RBC COMT activity is explained much better by codominant or 'intermediate' inheritance than by either dominant or recessive inheritance. The intermediate genetic model has also been used to analyze the data of Scanlon et al. [1979] on thermal inactivation of RBC COMT in a random sample of blood donors. Hypothesis tests based on this analysis confirm the conclusion of Scanlon et al. that individuals with different COMT genotypes differ in the thermostability of their RBC COMT. Using the RBC COMT activities of low-activity probands and their parents, we have derived the expected distribution of activity among the proband's sibs on the assumption of three genotypes in Hardy-Weinberg equilibrium in the population. The fit of this expected distribution to that observed is excellent, supporting the genetic model.

Original languageEnglish (US)
Pages (from-to)279-290
Number of pages12
JournalAmerican journal of medical genetics
Issue number3
StatePublished - 1981

ASJC Scopus subject areas

  • Genetics(clinical)


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