gms | German Medical Science

The present analysis aimed to determine whether a polymorphism in CYP3A5, encoding the major CYP3A enzyme in the human kidney is associated with blood pressure.

We examined a homogenous group of 115 young, caucasian male volunteers with normal blood pressure or mild never treated essential hypertension. Blood pressure was recorded by ambulatory 24-hour blood pressure monitoring and compared between individuals with high (*1/*3) and low (*3/*3) CYP3A5 expression. Moreover, genotype-dependent differences in parameters associated with the renin-angiotensin-aldosterone system were evaluated.

Individuals with the CYP3A5*3/*3 genotype had significantly higher 24 hour systolic blood pressure than subjects with the CYP3A5*1/*3 genotype (129±10 vs. 124±9 mmHg, p<0.05). Diastolic blood pressure was not different. There was no association of CYP3A5 genotype with angiotensin II plasma concentrations, renal plasma flow, glomerular filtration rate, urinary sodium excretion and parameters of cardiac structure and function as determined by echocardiography. Individuals with the CYP3A5*3/*3 genotype had significantly lower serum aldosterone levels than individuals with the CYP3A5*1/*3 genotype (101±29 vs. 117±29 pg/ml).

These data generated with a homogenous population of young Caucasians indicate that the CYP3A5 genotype affects blood pressure in humans possibly by genotype-dependent differences in renal, CYP3A5-mediated metabolism of cortisol and/or aldosterone. We interpret the lower serum aldosterone concentration in the genotype group with higher blood pressure as a counter-regulatory measure to attenuate the increased blood pressure associated with the CYP3A5*3/*3 genotype.