BACKGROUND: The polymorphic cytochrome P450 isoenzymes CYP2C9 and CYP2C19 are involved in the biotransformation of a wide variety of clinical drugs. Their major alleles occur with varying frequencies among different populations worldwide and have been associated with a varied capacity to degrade important therapeutic agents. This gives rise to important individual and interethnic variability in drug metabolism and may be the cause for different clinical responses regarding drug administration. In this study we aimed to analyze the distribution of the CYP2C9 and CYP2C19 major alleles associated with the impaired metabolism, and that account for the "poor metabolizer" phenotype in our study population. METHODS: A sample of 290 healthy subjects living in South Morocco was genotyped using a restriction fragment length polymorphism-polymerase chain reaction genotyping method. RESULTS: The CYP2C9*3 and CYP2C19*3 mutations were not found in our population. The CYP2C9*2 and CYP2C19*2 were the most common alleles, respectively with frequencies of 8% and 11.4%. Regarding CYP2C9*2 and CYP2C19*2, approximately 16% and 22% of Moroccans are respectively deficient metabolizers, and thus largely lack this enzymatic activity. Our results suggest that only CYP2C9*2 and CYP2C19*2 are likely to substantially contribute to individual and interethnic variability of CY2C9-19 activity in our population. CONCLUSIONS: The distribution of clinically relevant alleles of the CYP2C19 and CYP2C9 genes among our population follows the patterns commonly found in other Mediterranean populations, and suggests a certain degree of African influence. This population study provides relevant information on polymorphisms within the CYP2C19 and CYP2C9 genes. In the future, these results could be used in prognosis and for predicting response to drug treatments as well as to help develop personalized medicine studies in the Moroccan population.
BACKGROUND: The polymorphic cytochrome P450 isoenzymes CYP2C9 and CYP2C19 are involved in the biotransformation of a wide variety of clinical drugs. Their major alleles occur with varying frequencies among different populations worldwide and have been associated with a varied capacity to degrade important therapeutic agents. This gives rise to important individual and interethnic variability in drug metabolism and may be the cause for different clinical responses regarding drug administration. In this study we aimed to analyze the distribution of the CYP2C9 and CYP2C19 major alleles associated with the impaired metabolism, and that account for the "poor metabolizer" phenotype in our study population. METHODS: A sample of 290 healthy subjects living in South Morocco was genotyped using a restriction fragment length polymorphism-polymerase chain reaction genotyping method. RESULTS: The CYP2C9*3 and CYP2C19*3 mutations were not found in our population. The CYP2C9*2 and CYP2C19*2 were the most common alleles, respectively with frequencies of 8% and 11.4%. Regarding CYP2C9*2 and CYP2C19*2, approximately 16% and 22% of Moroccans are respectively deficient metabolizers, and thus largely lack this enzymatic activity. Our results suggest that only CYP2C9*2 and CYP2C19*2 are likely to substantially contribute to individual and interethnic variability of CY2C9-19 activity in our population. CONCLUSIONS: The distribution of clinically relevant alleles of the CYP2C19 and CYP2C9 genes among our population follows the patterns commonly found in other Mediterranean populations, and suggests a certain degree of African influence. This population study provides relevant information on polymorphisms within the CYP2C19 and CYP2C9 genes. In the future, these results could be used in prognosis and for predicting response to drug treatments as well as to help develop personalized medicine studies in the Moroccan population.
Entities:
Keywords:
CYP2C9 and CYP2C19 genes; South Moroccan population; drug metabolism; individual and interethnic variability; poor metabolizer (PM) phenotype