title: CYP3A5 as a candidate gene for hypertension: no support from an unselected indigenous West African population.
abstract: CYP3A5 (cytochrome P450, family 3, subfamily A, polypeptide 5) expression stimulates the sodium retentive actions of the mineralocorticoid receptor causative of hypertension, probably by means of its ability to substantially increase the level of 6β-hydroxylase activity. Most Black individuals are functional CYP3A5 expressers, and this is a candidate gene for the high incidence of hypertension in Black populations. The study investigates whether CYP3A5 expression results in higher blood pressure in a Ghanaian population. Real-time PCR was used to genotype 898 DNA samples for the CYP3A5*3 and CYP3A5*6 single-nucleotide polymorphisms with technically adequate genotyping for 881 samples. Of these, 803 were genetic CYP3A5 expressers, 44 nonexpressers and 34 uncertain (CYP3A5*3/*6). Although there was a trend in the proportion of hypertensive individuals as CYP3A5 expression decreased, using a two-sided t-test, no statistically significant relationship was established between systolic or diastolic pressure and CYP3A5*3 or CYP3A5*6 genotypes, or their haplotypes (Systolic confidence interval: -8.44 to -7.70, P=0.93, Diastolic confidence interval: -4.89 to 4.85, P=0.99). We conclude, therefore, that there is either no association between CYP3A5 expression and blood pressure or, if there is a relationship, the strength of the association is very small.
authors.affiliation: Analytical Services International Ltd, St George's, University of London, London, UK.
authors.forename: D L
authors.initials: DL
authors.lastname: Fisher
authors.affiliation: School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.|Komfo Anokye Teaching Hospital, Kumasi, Ghana.
authors.forename: J
authors.initials: J
authors.lastname: Plange-Rhule
authors.affiliation: Analytical Services International Ltd, St George's, University of London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Moreton
authors.affiliation: Institute of Medical and Biomedical Education: Renal Medicine, St George's, University of London, London, UK.
authors.forename: J B
authors.initials: JB
authors.lastname: Eastwood
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Kerry
authors.affiliation: Komfo Anokye Teaching Hospital, Kumasi, Ghana.
authors.forename: F
authors.initials: F
authors.lastname: Micah
authors.affiliation: Analytical Services International Ltd, St George's, University of London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Johnston
authors.affiliation: Division of Mental Health & Wellbeing, University of Warwick, Warwick Medical School, Coventry, UK.
authors.forename: F P
authors.initials: FP
authors.lastname: Cappuccio
authors.affiliation: Institute of Medical and Biomedical Education: Renal Medicine, St George's, University of London, London, UK.
authors.forename: I A M
authors.initials: IA
authors.lastname: MacPhee
mesh_terms: D000328:Adult; D000368:Aged; D044383:Black People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005869:Ghana / Q000453:epidemiology; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A