Major gene polymorphism for human erythrocyte (RBC) thiol methyltransferase (TMT)

Richard Arlen Price, Richard A. Keith, Richard S. Spielman, Richard M. Weinshilboum

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Thiol S-methylation is an important pathway in the metabolism of many sulfhydryl compounds including the antihypertensive drug captopril and the antirheumatic medication D-penicillamine. Erythrocyte (RBC) thiol methyltransferase (TMT) activity was measured in blood samples from 237 individuals from 49 nuclear families. Earlier studies have demonstrated familial aggregation of RBC TMT activity, suggesting a role for genetic determinants. Our study indicates the specific mode of inheritance and gives relative contributions of a major locus and background genotype. We found evidence for a major locus, TMT. The aliele frequencies for low enzyme activity, TMTL, and high activity TMTH, estimated from a power transformed scale were 0.58 and 0.42, respectively. The high activity allele, TMTH, appears to have reduced expression in heterozygous individuals (d = 0.21) and to act in concert with a strong influence from polygenic genotype (H = 0.75) to produce a highly heritable phenotype. This major gene polymorphism may now be studied using biochemical and molecular genetic techniques.

Original languageEnglish (US)
Pages (from-to)651-662
Number of pages12
JournalGenetic epidemiology
Issue number6
StatePublished - Jan 1 1989


  • RBC enzyme
  • complex segregation analysis
  • heritability

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)


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