Skip to main content Accessibility help

A Twin Study of Human Red Blood Cell Catechol-O-Methyl Transferase

  • Leon Grunhaus (a1), Richard Ebstein (a1), Robert H. Belmaker (a2), S. Gerald Sandler (a3) and Wulff Jonas (a4)...


Significant sibling-sibling and within-family correlations of human red blood cell catechol-o-methyl transferase activity have suggested a high degree of genetic control over levels of activity of this catecholamine-related enzyme. However, family studies do not disentangle genetic from environmental similarities as causative of within-family correlations. We therefore undertook a human twin study using the monozygotic-dizygotic comparison method. Twelve pairs of monozygotic twins had an intraclass correlation of .90 in red blood cell catechol-o-methyl transferase activity, and seven pairs of dizygotic twins had an intraclass correlation of .37. Heritability of the enzyme activity was estimated by different methods as between 68–100 per cent.



Hide All
Axelrod, J. (1966) Mcthylation reactions in the formation and metabolism of catecholamines and other biogenic amines. Pharmacological Review, 18, 95113.
Axelrod, J. & Cohn, C. K. (1971) Methyl transferase enzymes in red blood cells. Journal of Pharmacology and Experimental Therapeutics, 176, 650–4.
Briggs, M. H. & Briggs, M. (1973) Hormonal influences on erythrocyte catechol-o-methyl transferase activity in humans. Experientia, 29, 278.
Cohn, G. K., Dunner, D. L. & Axelrod, J. (1970) Reduced catechol-o-methyl transferase activity in red blood cells of women with primary affective disorders. Science, 170, 1323–4.
Cohn, G. K., & Wintmare, R. (1972) Probable nutritional basis for effect of estradiol on rat liver catechol-o-methyl transferase. Life Sciences, 1, 11, 581–5.
Dorus, E., Pandey, G. N., Frazer, A. & Mendels, J. (1974) Genetic determinant of lithium ion distribution. Archives of General Psychiatry, 31, 463–5.
Dunner, D. L., Cohn, G. K., Gershon, E. S. & Goodwin, R. (1971) Differential catechol-o-methyl transferase activity in unipolar and bipolar affective illness. Archives of General Psychiatry, 25, 348–53.
Falconer, D. S. (1960) Introduction to Quantitative Genetics. New York: Ronald Press.
Gershon, E. S. & Jonas, W. Z. A clinical and genetic study of erythrocyte catechol-o-methyl transferase activity in primary affective disorder. Archives of General Psychiatry. In press.
Hertting, G. & Axelrod, J. (1961) Fate of tritiated norepinephrine at the sympathetic nerve ending. Nature, 192, 172–3.
Jensen, A. R. (1967) Estimation of the limits of heritability of traits by comparison of monozygotic and dizygotic twins. Proceedings of the National Academy of Science, 58, 149–56.
Jonas, W. Z. & Gershon, E. S. (1974) A method for determination of catechol-o-methyl transferase in red blood cells. Clinica Chimica Acta, 54, 391–4.
Marsden, C. A., Broch, O. J. Jr. & Guldbero, H. C. (1971) Catechol-o-methyl transferase and monoamine oxidase activities in rat submaxillary gland. Effects of ligation, sympathectomy and some drugs. European Journal of Pharmacology, 15, 335–42.
Newman, H. H., Freeman, F. N. & Holzinger, K. J. (1937) Twins: A Study of Heredity and Environment. Chicago: University of Chicago Press.
Nichols, R. G. (1965) The National Merit Twin Study. In Methods and Goals in Human Behaviour Genetics (Vandenburg, ed. S. G.), p. 231. New York: Academic Press.
Nichols, R. G. & Bilbro, W. C. Jr. (1966) The diagnosis of twin zygosity. Acta Genetica, Basel, 16, 265–75.
Nies, A., Robinson, D. S., Lamborn, K. R. & Lampert, R. P. (1973) Genetic control of platelet and plasma monoamine oxidase activity. Archives of General Psychiatry, 28, 834–8.
Osborne, R. H. & De George, F. V. (1959) Genetic Basis of Morphologic Variation: An Evaluation and Application of the Twin Study Method. Cambridge, Mass.: Harvard University Press.
Parvez, H. & Parves, S. (1973) The effects of metopirone and adrenalectomy on the regulation of the enzymes monoamine oxidase and COMT in different brain regions. Journal of Neurochemistry, 20, 1011–20.
Rosenthal, D. (1970) Genetic Theory and Abnormal Behaviour. New York: McGraw-Hill.
Ross, S. B., Wetterberg, L. & Myrhed, M. (1973) Genetic control of plasma dopamine-B-hydroxylase. Life Sciences, 1, 12, 529–32.
Schildkraut, J. J. (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. American Journal of Psychiatry, 122, 509–22.
Sharpless, N. S., Tyce, G. M. & Owen, G. A. (1973) Effect of chronic administration of L-dopa on catechol-o-methyl transferase in rat tissues. Life Sciences, 1, 12, 97106.
Weinshilboum, R. M., Elveback, L. R. & Weidman, W. H. (1974) Red blood cell catechol-o-methyl transferase activity: sibling-sibling correlations. Nature, 252, 490–1.
Webs, J. L., Cohn, C. K. & Chase, T. N. (1971) Reduction of catechol-o-methyl transferase activity by chronic L-dopa administration. Nature, 234, 218–19.
Wyatt, R. J., Murphy, D. L., Belmaker, R., Cohen, S. Donnelly, C. H. & Pollin, W. (1973) Reduced monoamine oxidase in platelets: a possible genetic marker for vulnerability to schizophrenia. Science, 179, 916–18.


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

A Twin Study of Human Red Blood Cell Catechol-O-Methyl Transferase

  • Leon Grunhaus (a1), Richard Ebstein (a1), Robert H. Belmaker (a2), S. Gerald Sandler (a3) and Wulff Jonas (a4)...
Submit a response


No eLetters have been published for this article.


Reply to: Submit a response

Your details

Conflicting interests

Do you have any conflicting interests? *