The metabolism of irinotecan involves sequential activation to SN-38 and detoxification to the pharmacologically inactive SN-38 glucuronide. Previous results have demonstrated the role of UGT1A1 in the glucuronide of SN-38 and a significant correlation between in vitro glucuronidation of SN-38 and UGT1A1 gene promoter polymorphism. Results from Iyer et al (pages 43–47) suggest that screening for UGT1A1*28 polymorphism may identify patients with lower SN-38 glucuronidation rates and greater susceptibility to irinotecan-induced gastro-intestinal and bone marrow toxicity.
SULT2A1 catalyze the sulfate conjugation of dehydroepiandrosterone as well as other steroids. In their paper, Thomae et al (pages 48–56) have resequenced SULT2A1 using 60 DNA samples from African-American and 60 samples from Caucasian-American subjects and observed that common genetic polymorphisms for SULT2A1 can result in reductions in levels of both activity and enzyme protein. They also raise the possibility of ethnic specific pharmacogenetic variation in SULT2A1-catalyzed sulfation of both endogenous and exogenous substrates for this phase II drug metabolising enzyme.
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