GLUTATHIONE S-TRANSFERASE-MU POLYMORPHISM DOES NOT EXPLAIN VARIATION IN NITROGLYCERIN RESPONSIVENESS

Objective: To determine whether the considerable interindividual varia bility in nitroglycerin-induced venodilation in humans is related to t he polymorphic expression of the mu class of glutathione S-transferase (GSTmu). Recently vascular glutathione S-transferase (EC 2.5.1.18) of the mu-class (GSTmu), a polymorphic group of enzymes present in only about 60% of the population, have been identified and shown in vitro t o possess high metabolic activity toward nitroglycerin. Their clinical relevance is unknown. Design: Dose-response relationships to nitrogly cerin were constructed in vivo measuring changes in compliance of dors al hand veins in 26 healthy volunteers during local infusion of small amounts of nitroglycerin. Polymerase chain reaction was applied to det ect the deoxyribonucleic acid sequence that codes GSTmu in whole blood samples. Results: The GSTmu isozyme was present in 15 subjects (58%) and deficient in 11 subjects. Values for mean maximum venodilation (E( max)) and dose rates producing 50% of E(max) (ED50) were not significa ntly different between the groups with or without GSTmu. The respectiv e values were 98% and 103% dilation for E(max) and 9 and 16 ng/min for ED50. There was no gender difference in the venodilatory response to nitroglycerin. Conclusions: Subjects lacking GSTmu can clearly respond normally to nitroglycerin, and the large interindividual variability in nitroglycerin potency is not related to the expression of this poly morphic enzyme. Intersubject variability is therefore more likely to b e the result of differences in the presence or activity of other vascu lar enzymes or in steps further distal in the venodilatory cascade.