Higher activity of polymorphic thiopurine S-methyltransferase in erythrocytes from neonates compared to adults.
Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including thiopurine antimetabolites (i.e. mercaptopurine and thioguanine). The activity of TPMT in erythrocytes and other tissues exhibits genetic polymorphism, which is inherited as an autosomal codominant trait. Although inheritance is the principal determinant of TPMT activity, other factors (e.g. renal function, race and thiopurine therapy) have been shown to influence erythrocyte TPMT activity. Because the TPMT polymorphism has not been established in early erythrocyte populations, and the activity of many enzymes differs in neonates, we determined the activity of TPMT in erythrocytes obtained from 60 full-term newborns. Median peripheral blood TPMT activity was 25.3 U per ml pRBC (range 9-52.8 U per ml pRBC), which was > 50% higher than race matched healthy adults (p < 0.001). Western blot analysis demonstrated higher TPMT protein content in erythrocytes from newborns compared to adults, and revealed a significant correlation between TPMT protein and TPMT activity in erythrocytes (rs = 0.63, p = 0.03). Although erythrocyte TPMT activity was significantly higher in newborns, the distribution of activity in newborns was consistent with the genetic polymorphism previously observed in adults.
McLeod
H L
HL
Pharmaceutical Department, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Krynetski
E Y
EY
Wilimas
J A
JA
Evans
W E
WE
D000328:Adult; D000375:Aging / Q000378:metabolism*; D044383:Black People / Q000235:genetics; D015153:Blotting, Western; D004912:Erythrocytes / Q000201:enzymology*; D005312:Fetal Blood / Q000201:enzymology; D006801:Humans; D007231:Infant, Newborn; D008780:Methyltransferases / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D012016:Reference Values; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
D008780:Methyltransferases; C022745:thiopurine methyltransferase