title: Thiol methylation pharmacogenetics: heritability of human erythrocyte thiol methyltransferase activity.
abstract: Thiol methylation of aliphatic sulfhydryl drugs is catalyzed by thiol methyltransferase (TMT), an enzyme activity that can be measured in the human erythrocyte (RBC) membrane. As a first step toward determining the possible role of inheritance in the regulation of individual variations in the S-methylation of drugs in man, the heritability of human RBC membrane TMT activity was determined. RBC TMT activity was measured in blood samples from 231 first-degree relatives in 47 randomly selected families. The frequency distribution of enzyme activities was unimodal, with a fivefold variation within +/- 2 SDs. RBC TMT activity did not correlate with either age or sex. Heritability in the "narrow" sense (h2) was estimated by comparing correlations of RBC TMT activities in first-degree relatives with theoretical values expected for a trait under total additive genetic control. The correlation between RBC TMT activities in mothers and fathers in these families was only 0.04, a finding that made shared environment a less likely explanation for significant correlations among other family members. However, sibling-sibling (S-S), parent-offspring (P-O), and midparent (average of two parental values)-offspring (M-O) correlations were 0.49, 0.49, and 0.69.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011897:Random Allocation
chemical_list: D008780:Methyltransferases; C022742:thiol S-methyltransferase