Genetic Polymorphisms of CYP2C9

Abstract

Background: There is little knowledge about genotyping of cytochrome P450s in the Middle East, and there has not been any report on the genotype of CYP2C9 allelic variants in Lebanese population . Aims and objectives: The purpose of the study was to determine and compare the frequencies of the cytochrome P450 CYP2C9 variants in the Lebanese population with the frequencies in other ethnic populations. Methods: CYP2C9 genotypes were determined in a total of 146 samples of unrelated, healthy Lebanese individua ls residing in different areas in Lebanon. Fo llowing DNA extrac- tion from buccal cells and polymerase chain reaction, genotyping was performed by Pyrosequencing method. CYP2C9 genotypes results were compared to other populations’; i.e., Middle Easterns, Europeans, Asians, and African Ameri- cans. Results and discussion: The frequencies of the CYP2C29*2, CYP2C9*3, and CYP2C9*4 alleles were 11.305%, 11.645%, and 1.025% respectively. No CYP2C9*5 allele variants were found among the Lebanese study sample. Vol- unteers could be divided into three CYP2C9 genotype groups: subjects (76.71%) with no mutated alleles (CYP2C9*1*1; homozygous extensive metabolizers, EM), 21.23% with one mutated allele (CYP 2C9*1*2, *1*3, *1*4, and *1*5; het- erozygous intermediate metabolizers IM), and 2.06% with two mutated alleles, homozygous variants as poor metabo- lizers, PM). The comparative analysis using genotyp e groups of different populations showed differences among Leba- nese and other Caucasians. Conclusion: This is the first report from Lebanon on CYP2C9 variants; it highlights a higher frequency of CYP2C9 extensive metabolizers compared to other populations including Caucasians. The results serve as a database on CYP 2C9 polymorphisms and baseline clinica l data for dosing and avoiding adverse drug reac- tions of drugs met a bol i s ed by CYP2C9 in Lebanese patien