title: Major gene polymorphism for human erythrocyte (RBC) thiol methyltransferase (TMT).
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, 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.
authors.affiliation: Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: R A
authors.initials: RA
authors.lastname: Price
authors.forename: R A
authors.initials: RA
authors.lastname: Keith
authors.forename: R S
authors.initials: RS
authors.lastname: Spielman
authors.forename: R M
authors.initials: RM
authors.lastname: Weinshilboum
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000201:enzymology*; D005190:Family; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D008780:Methyltransferases; C022742:thiol S-methyltransferase