CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults

Abstract

A single-nucleotide polymorphism (A6986G) in the cytochrome P-450 3A5 ( CYP3A5) gene distinguishes an expressor ( *1) and a reduced-expressor ( *3) allele and largely predicts CYP3A5 content in liver and intestine. CYP3A5 is the prevailing CYP3A isoform in kidney. We report that, among renal microsomes from 21 organ donors, those from *1/ *3 individuals had at least eightfold higher mean kidney microsomal CYP3A5 content and 18-fold higher mean CYP3A catalytic activity than did those from *3/ *3 individuals ( P = 0.0001 and P = 0.0137, respectively). We also report significant associations between the A6986G polymorphism and systolic blood pressure ( P = 0.0007), mean arterial pressure ( P = 0.0075), and creatinine clearance ( P = 0.0035) among 25 healthy African-American adults. These associations remained significant when sex, age, and body mass index were taken into account. The mean systolic blood pressure of homozygous CYP3A5 expressors ( *1/ *1) exceeded that of homozygous nonexpressors ( *3/ *3) by 19.3 mmHg. We speculate whether a high CYP3A5 expressor allele frequency among African-Americans may contribute to a high prevalence of sodium-sensitive hypertension in this population.