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Abstract
Nilotinib is a BCR-ABL inhibitor used in CML treatment. Although it is metabolized mainly by CYP3A4, yet UGT1A1 is recently believed to play also a role. As CYP3A4*1B and UGT1A1*28 polymorphisms were proved to decrease CYP3A4 and UGT1A1 enzymatic activity, therefore, a there may be a possible association between these polymorphisms and the inter-individual variability in response to nilotinib treatment, as well as, the occurrence of adverse events, such as hyperbilirubinemia. Moreover, nilotinib inhibits the sole enzyme responsible for bilirubin metabolism, which is UGT1A1; this may result in hyperbilirubinemia that was suggested by studies to be more pronounced in those having UGT1A1*28. This research was conducted on Egyptian CML patients administered nilotinib to study the frequency of CYP3A4*1B and UGT1A1*28 polymorphisms, and the potential association between UGT1A1/CYP3A4 genotypes and the molecular response to nilotinib treatment, as well as, hyperbilirubinemia. The blood samples of 67 patients at National Cancer Institute were used to isolate DNA and the polymorphisms were detected using HRM and PCR-RFLP. Bilirubin levels (post-treatment) and molecular response after 3, 6, and 12 months of nilotinib treatment were also assessed. Our results showed that the percentage of patients with CYP3A4*1B and UGT1A1*28 alleles was 10.6% and 28.4%, respectively. Also, no significant association was found between any of CYP3A4 or UGT1A1 genotypes and hyperbilirubinemia nor with the molecular response after 3, 6, and 12 months. Therefore, we concluded that the differences in CYP3A4 and UGT1A1 genotypes do not influence the response nor the hyperbilirubinemia incidence in the studied Egyptian patients