CYP3A5 genotype is associated with diagnosis of hypertension in elderly patients: data from the DEBATE Study.
OBJECTIVE
The aim of this study was to address the presently controversial question of whether cytochrome P450 (CYP) 3A5 polymorphism is associated with hypertension.


METHODS
We studied 373 elderly (age > or =75 years) Finnish (Caucasian) patients from the ongoing DEBATE (Drugs and Evidence Based Medicine in the Elderly) trial. The patients were classified into those with a history of hypertension (n = 229) and those without a history of hypertension (n = 144) on the basis of a detailed questionnaire on each patient's medical history and an interview. The patients were genotyped for the CYP3A5 6986A/G single nucleotide polymorphism (SNP) [CYP3A5*1/*3 alleles].


RESULTS
The proportion of individuals with the CYP3A5*1/*3 genotype, i.e. CYP3A5 expressors, was significantly higher among patients with a diagnosis of hypertension than among patients without (18.3% vs 9.0%, p = 0.016). The corresponding odds ratio was 2.26 (95% CI 1.17, 4.38). The allele and genotype frequencies for the two control SNPs, ABCB1 (MDR1) 3435C/T and SLCO1B1 521T/C, did not differ between the two groups.


CONCLUSIONS
This work lends support to the theory that the polymorphic CYP3A5 enzyme may be involved in regulation of blood pressure. The possible role of CYP3A5 as a genetic contributor to hypertension susceptibility warrants further study.
Kivistö
Kari T
KT
Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. kari.kivisto@ikp-stuttgart.de
Niemi
Mikko
M
Schaeffeler
Elke
E
Pitkälä
Kaisu
K
Tilvis
Reijo
R
Fromm
Martin F
MF
Schwab
Matthias
M
Lang
Florian
F
Eichelbaum
Michel
M
Strandberg
Timo
T
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001483:Base Sequence; D001794:Blood Pressure / Q000235:genetics; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000235:genetics; D019317:Evidence-Based Medicine; D005260:Female; D005387:Finland; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
D004247:DNA; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A