Abstract
BackgroundGenetic influences on drug efficacy and tolerability are now widely known. Pharmacogenetics has thus become an expanding field with great potential for improving drug efficacy and reducing toxicity. Many pharmacologically-relevant polymorphisms do show variability among different populations. Knowledge of allelic frequency distribution within specified populations can be useful in explaining therapeutic failures, identifying potential risk groups for adverse drug reactions (ADRs) and optimising doses for therapeutic efficacy. We sought to determine the prevalence of clinically relevant Cytochrome P450 (CYP) 2C8, CYP2C9, and CYP2C19 variants in Ghanaians. We compared the data with other ethnic groups and further investigated intra country differences within the Ghanaian population to determine its value to pharmacogenetics studies.MethodsRFLP assays were used to genotype CYP2C8 (*2, *3, *4) variant alleles in 204 unrelated Ghanaians. CYP2C9*2 and CYP2C19 (*2 and *3) variants were determined by single-tube tetra-primer assays while CYP2C9 (*3, *4, *5 and *11) variants were assessed by direct sequencing.ResultsAllelic frequencies were obtained for CYP2C8*2 (17%), CYP2C8*3 (0%), CYP2C8*4 (0%), CYP2C9*2 (0%), CYP2C9*3 (0%), CYP2C9*4 (0%), CYP2C9*5 (0%), CYP2C9*11 (2%), CYP2C19*2 (6%) and CYP2C19*3 (0%).ConclusionAllele frequency distributions for CYP2C8, CYP2C9 and CYP2C19 among the Ghanaian population are comparable to other African ethnic groups but significantly differ from Caucasian and Asian populations. Variant allele frequencies for CYP2C9 and CYP2C19 are reported for the first time among indigenous Ghanaian population.
Highlights
Genetic influences on drug efficacy and tolerability are widely known
Some areas of the world especially indigenous African populations have scarcity information in the current pharmacogenetics research [1,2] Cytochrome P450 2C (CYP2C) subfamily of enzymes form 18-30% of human CYPs and metabolises nearly 20% of all therapeutic drugs commonly prescribed in clinical practice [3]
CYP2C9 polymorphisms have been associated with an increase risk of bleeding in patients treated with standard doses of warfarin [11] while phenytoin toxicity has been reported in some patients [12]
Summary
Genetic influences on drug efficacy and tolerability are widely known. Pharmacogenetics has become an expanding field with great potential for improving drug efficacy and reducing toxicity. CYP2C8, CYP2C9, and CYP2C19 enzymes constitute 26%, 50%, and 16% respectively of the CYP2C subfamily [5] They are polymorphically expressed with variable allele frequencies among different ethnic populations [2,6,7], Some of these CYP2C variant alleles have been associated with either an increased or decreased metabolism of several clinically important drugs [3,5,8,9]. Some of these drugs have narrow therapeutic index and have been involved in the development of adverse side effects. The U.S FDA has added genetic information to prescribing information on some of these drugs such as Warfarin, carbamazepine and codeine to assist prescribers safely achieve therapeutic doses http://www.fda.gov/Drugs/ScienceResearch/Resear chAreas/Pharmacogenetics/ucm083378.htm
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