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

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 allele frequencies for low enzyme activity, TMT(L), and high activity TMT(H), estimated from a power transformed scale were 0.58 and 0.42, respectively. The high activity allele, TMT(H), 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
Volume6
Issue number6
StatePublished - 1989

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thiol S-methyltransferase
Genes
Sulfhydryl Compounds
Molecular Biology
Genotype
Genetic Techniques
Penicillamine
Captopril
Nuclear Family
Gene Frequency
Methylation
Antihypertensive Agents
Erythrocytes
Alleles

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

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Major gene polymorphism for human erytrocyte (RBC) thiol methyltransferase (TMT). / Price, R. A.; Keith, R. A.; Spielman, R. S.; Weinshilboum, Richard M.

In: Genetic Epidemiology, Vol. 6, No. 6, 1989, p. 651-662.

Research output: Contribution to journalArticle

Price, R. A. ; Keith, R. A. ; Spielman, R. S. ; Weinshilboum, Richard M. / Major gene polymorphism for human erytrocyte (RBC) thiol methyltransferase (TMT). In: Genetic Epidemiology. 1989 ; Vol. 6, No. 6. pp. 651-662.
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