Unraveling of the genetic polymorphism for ultra-rapid metabolism of phenytoin / Fazleen Haslinda Mohd Hatta , Prof Madya Dr The Lay Kek , Prof Dr Mohd Zaki Salleh

• Main Authors: Mohd Hatta, Fazleen Haslinda, Teh, Lay Kek, Salleh, Mohd Zaki
• Format: Research Reports
• Language: English
• Published: Research Management Institute , Universiti Teknologi MARA 2010
• Subjects: Drugs and their actions
• Online Access: https://ir.uitm.edu.my/id/eprint/6429/1/LP_FAZLEEN%20HASLINDA%20MOHD%20HATTA%2010_24.pdf; https://ir.uitm.edu.my/id/eprint/6429/

The frequency of functionally important mutations and alleles of genes coding for CYP2C9 metabolizing enzymes shows a wide ethnic variation. However, little is known of the frequency distribution of the minor allelic variants that could explain other metabolic capacity. Methods: Using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) genotyping assays and allele specific PCR, the frequencies of three variants of the cytochrome P450 (CYP) 2C9 were determined in a sample of 93 CYP2C9 *1/*1 Swedish volunteers and 128 CYP2C9 *1/*1 Korean volunteer. The genotyping results were then compared to their Losartan metabolic ratio to find if there is a genotype-phenotype relationship. Results: Three of the mutations were significantly lower in the Korean population. Mutation in intron 1 + 83 bp occurred in 0.78% (Korean) and 23.11% (Swedes) of alleles while the mutation at exon 2 +73 bp occurred in 0.78% (Korean) and 22.58% (Swedes) of alleles while mutation in intron 6 + 95 bp occurs at 0.78% (Korean) and 27.96% (Swedes) of alleles. The most homogeniously spread mutation ethnically, occurring in intron 8 - 109 bp occurs at 37.11% (Korean) and 31.72% (Swedes) of alleles. Conclusion: The overview of different allele variation distribution of metabolizing enzymes among two different populations shows interesting results. The gathered information is inconclusive to explain the ultrarapid metabolizer, but it show that there is some ethnically differences that may lead to differences in metabolism capacity.