Prevalence of the genetic mutation Cyp2c8*5 in selected ethnic groups in Southern Ghana

Loading...
Thumbnail Image
Date
2015-11-16
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Effects of genetic variability on drug efficacy and tolerability are important. Many pharmacologically-relevant genetic polymorphisms show variability in different populations. Information on allelic frequency is useful in identifying adverse drug reaction (ADRs) risk populations, understanding therapeutic failures and optimising doses for efficacy and efficiency. CYP2C8 are clinically important haem-containing group of enzymes which metabolize several drugs (e.g. anti-malarial, anti-diabetic, anti-cancer, non-steroidal anti-inflammatory) and endogenous substances (e.g. alltrans- retinoic acid, steroidal hormones and arachidonic acid). CYP2C8*5 homozygous individuals are poor metabolizers with increased risk of drug toxicity. The study determined prevalence of clinically relevant cytochrome P450 (CYP) 2C8*5 polymorphism in 80 unrelated individuals, 10 each from the ethnic groups Akyem, Ashanti, Anlo, Ewe, Fanti, Ga, Krobo and Nzema in Southern Ghanaian population. Medical history on adverse drug reactions of the subjects and level of dependency on drugs metabolized by CYP2C8 enzyme was obtained by questionnaire. Allele Specific-PCR analyses were used to genotype CYP2C8*5 alleles in the study subjects. Allelic frequency for CYP2C8*5 was 0.8375 which was statistically significant (p<0.05). There was no significant difference (p> 0.05) in the prevalence of CYP2C8*5 allele within the ethnic groups. Also, there was no significant association (p >0.05) between CYP2C8*5 allele and reported ADRs. Many (88.75%) of the study subjects depended highly (>1-3x in a year) on drugs metabolized by CYP2C8. The study population may be at risk of toxicity in using drugs metabolized by CYP2C8 because of the high prevalence determined since CYP2C8*5 mutants have been reported to have a reduced enzymatic activity.
Description
A thesis submitted to the Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology in partial fulfillment of the requirement for the Degree of Master of Philosophy in Biochemistry.
Keywords
Citation