Genotyping of CYP2C9 for cardiovascular patients / Norshazareen Abd Manab

• Main Author: Abd Manab, Norshazareen
• Format: Thesis
• Language: English
• Published: 2005
• Subjects: RM Therapeutics. Pharmacology; RS Pharmacy and materia medica
• Online Access: https://ir.uitm.edu.my/id/eprint/98633/1/98633.PDF; https://ir.uitm.edu.my/id/eprint/98633/

CYP2C9 lines the important drug-metabolizing cytochrome P450 isoforms in the human liver but linked with inter-individual variation in drug-response relationship due to single nucleotide polymorphism of the encoding gene. Modification of CYP2C9 activity due to genetic factor alters the metabolism of drug substrates resulting in reduced efficacy or worse, toxicity. Amongst substrates of CYP2C9, warfarin is of special interest due to its narrow therapeutic index. The objective of this study is to determine the type and frequency of CYP2C9 polymorphism among patients on warfarin therapy. We successfully genotyped 180 patients who were on warfarin from 183 samples. The genomic DNA was obtained from the gene pool of Universiti Teknologi Mara Pharmacogenomic Research Group.The DNA was genotyped for known CYP2C9 polymorphic allelic (CYP2C9*2, *3 and *7) variants with the use of allele specific multiplex polymerase chain reaction and the product was resolved via gel electrophoresis. Polymorphic variants of CYP2C9 (CYP2C9*2 and CYP2C9*4) were not detected in these patients. Among the 180 patients, the genotype frequency of CYP2C9*1/*1 was 92.7% and CYP2C9*l/*3 was 7.3%. There was only two genotype expressed in patients on warfarin therapy, CYP2C9*1/*1 and CYP2C9*l/*3. This provide a useful database to help physician predict the possibility of adverse drug reaction among patients on warfarin in Malaysia.