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Major gene polymorphism for human erythrocyte (RBC) thiol methyltransferase (TMT)
Author(s) -
Price Richard Arlen,
Keith Richard A.,
Spielman Richard S.,
Weinshilboum Richard M.,
Vogler G. P.,
Rao D. C.
Publication year - 1989
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.1370060602
Subject(s) - allele , genotype , methyltransferase , locus (genetics) , genetics , biology , gene , polymorphism (computer science) , methylation , microbiology and biotechnology
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, 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.