CYP3A5 genotype is associated with elevated blood pressure.
The present study aimed to determine whether a polymorphism in CYP3A5, encoding the major CYP3A enzyme in the human kidney, is associated with blood pressure in Caucasians. A homogenous group of 115 young, white male students with normal or mildly elevated, but untreated blood pressure was included. Blood pressure was recorded by ambulatory 24-h blood pressure-monitoring and compared between individuals with high (*1/*3) and low CYP3A5 expression (*3/*3). Moreover, genotype-dependent differences in parameters associated with the renin-angiotensin-aldosterone system were evaluated. Twenty-four hour diastolic blood pressure values were not significantly different between the two groups. However, individuals with the CYP3A5*3/*3 genotype had significantly higher 24-h ambulatory systolic blood pressure values compared to subjects with the CYP3A5*1/*3 genotype (129+/-10 versus 124+/-9, P < 0.05). There was no association of CYP3A5 genotype with angiotensin II plasma concentrations, renal plasma flow, glomerular filtration rate, urinary sodium excretion and parameters determined by echocardiography, but the *3/*3 group had significantly lower serum aldosterone concentrations compared to the individuals with the *1/*3 genotype (101+/-29 versus 117+/-29 pg/ml, P < 0.05). These data, as 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 the elevated systolic blood pressure as a counter-regulatory mechanism to attenuate the increased blood pressure associated with the CYP3A5*3/*3 genotype.
Fromm
Martin F
MF
Institute of Clinical and Experimental Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen, Germany.
Schmidt
Bernhard M W
BM
Pahl
Andreas
A
Jacobi
Johannes
J
Schmieder
Roland E
RE
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000235:genetics*; D018660:Blood Pressure Monitoring, Ambulatory; D016022:Case-Control Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D016277:Ventricular Function, Left; D044465:White People
D000804:Angiotensin II; D000450:Aldosterone; D003577:Cytochrome P-450 Enzyme System; D012964:Sodium; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D012083:Renin