ObjectiveThe aim of this study was to address the presently controversial question of whether cytochrome P450 (CYP) 3A5 polymorphism is associated with hypertension.MethodWe studied 373 elderly (age ≥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 theCYP3A56986A/G single nucleotide polymorphism (SNP) [CYP3A5*1/*3 alleles].ResultsThe proportion of individuals with theCYP3A5*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 andSLCO1B1521T/C, did not differ between the two groups.ConclusionThis work lends support to the theory that the polymorphic CYP3A5 enzyme may be involved in regulation of blood pressure. The possible role ofCYP3A5as a genetic contributor to hypertension susceptibility warrants further study.