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 CYP 2C9 allelic variants in Lebanese population. Aims and objectives:...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 CYP 2C9 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 individuals residing in different areas in Lebanon. Following DNA extraction 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 Americans. 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 (CYP 2C9*1*1;homozygous extensive metabolizers, EM), 21.23% with one mutated allele (CYP 2C9*1*2, *1*3, *1*4, and *1*5;heterozygous intermediate metabolizers IM), and 2.06% with two mutated alleles, homozygous variants as poor metabolizers, PM). The comparative analysis using genotype 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 clinical data for dosing and avoiding adverse drug reac- tions of drugs metabolised by CYP2C9 in Lebanese patients.展开更多
文摘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 CYP 2C9 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 individuals residing in different areas in Lebanon. Following DNA extraction 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 Americans. 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 (CYP 2C9*1*1;homozygous extensive metabolizers, EM), 21.23% with one mutated allele (CYP 2C9*1*2, *1*3, *1*4, and *1*5;heterozygous intermediate metabolizers IM), and 2.06% with two mutated alleles, homozygous variants as poor metabolizers, PM). The comparative analysis using genotype 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 clinical data for dosing and avoiding adverse drug reac- tions of drugs metabolised by CYP2C9 in Lebanese patients.
