TY - JOUR
T1 - Major gene polymorphism for human erythrocyte (RBC) thiol methyltransferase (TMT)
AU - Price, Richard Arlen
AU - Keith, Richard A.
AU - Spielman, Richard S.
AU - Weinshilboum, Richard M.
PY - 1989/1/1
Y1 - 1989/1/1
N2 - 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.
AB - 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.
KW - RBC enzyme
KW - complex segregation analysis
KW - heritability
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U2 - 10.1002/gepi.1370060602
DO - 10.1002/gepi.1370060602
M3 - Article
C2 - 2606339
AN - SCOPUS:0024840113
SN - 0741-0395
VL - 6
SP - 651
EP - 662
JO - Genetic epidemiology
JF - Genetic epidemiology
IS - 6
ER -