Development of a PCR method for detection of UGTJAJ polymorphism / Khairul Muhaimin Othman
Irinotecan is a camptothecin analog with potent antitumor activity resulting from the inhibition of topoisomerase. Dose-limiting toxicity of irinotecan includes severe leukopenia, neutropenia and diarrhea. Genetic polymorphisms of UDP glucuronosyltransferase (UGT) lAl, a key metabolizing enzyme of...
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| Format: | Thesis |
| Language: | English |
| Published: |
2007
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| Subjects: | |
| Online Access: | https://ir.uitm.edu.my/id/eprint/99883/1/99883.PDF |
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| Summary: | Irinotecan is a camptothecin analog with potent antitumor activity resulting from the inhibition of topoisomerase. Dose-limiting toxicity of irinotecan includes severe leukopenia, neutropenia and diarrhea. Genetic polymorphisms of UDP glucuronosyltransferase (UGT) lAl, a key metabolizing enzyme of irinotecan, are important determinants of individual variations in susceptibility to toxicity. Pharmacogenomic studies of irinotecan toxicity have therefore focused on genetic polymorphisms of the UGTJAJ gene. This project aimed to develop a simple PCR test to identify genetic variants of UGTJAI and mainly focus on UGTJAJ *6 and UGTJAJ *27, single nucleotide polymorphisms in exon 1 of the UGTJAJ gene that are found mainly in Asian. The allele specific PCR amplification was chosen to be studied because it is suitable for the detection of single nucleotide polymorphism within the gene. In this study, method was optimized only for detection of *27 allele but not for *6 allele. Problem with the primer designed for amplification of *6 allele was thought to be the possible reason for not able to optimize the method for *6 allele. Pipetting error also could be one of the reason for unsuccessful amplification process. Further study should be carried out to continue this beneficial research. This PCR method can also be commercialized as a tool for individualization of pharmacotherapy especially anti-cancer therapy once the method is fully optimized and validated as it is cost and time saving in patient management due to reduced effort spent in trial and error procedure. |
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