HIGHER ACTIVITY OF POLYMORPHIC THIOPURINE S-METHYLTRANSFERASE IN ERYTHROCYTES FROM NEONATES COMPARED TO ADULTS

Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of a romatic and heterocyclic sulfhydryl compounds, including thiopurine an timetabolites (i.e. mercaptopurine and thioguanine), The activity of T PMT in erythrocytes and other tissues exhibits genetic polymorphism, w hich is inherited as an autosomal codominant trait, Although inheritan ce is the principal determinant of TPMT activity, other factors (e.g. renal function, race and thiopurine therapy) have been shown to influe nce erythrocyte TPMT activity, Because the TPMT polymorphism has not b een established in early erythrocyte populations, and the activity of many enzymes differs in neonates, we determined the activity of TPMT i n 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 pR BC), which was > 50% higher than race matched healthy adults (p < 0.00 1), Western blot analysis demonstrated higher TPMT protein content in erythrocytes from newborns compared to adults, and revealed a signific ant correlation between TPMT protein and TPMT activity in erythrocytes (r(s) = 0.63, p = 0.03). Although erythrocyte TPMT activity was signi ficantly higher in newborns, the distribution of activity in newborns was consistent with the genetic polymorphism previously observed in ad ults.