Prevalence of the genetic mutation Cyp2c8*5 in selected ethnic groups in Southern Ghana
Loading...
Date
2015-11-16
Authors
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.