Association between the CYP3A5 genotype and blood pressure.
We tested the hypothesis that the presence of a CYP3A5*1 allele is associated with increases in blood pressure in 2 studies of subjects with a total of 683 participants. The first study involving 271 subjects was part of a longitudinal study conducted at Indiana University Medical Center that consisted of 2 phases. The first phase studied the relationship of salt sensitivity with blood pressure, whereas the second phase, conducted approximately 26 years later, studied the relationship between blood pressure, carbohydrate intolerance, and vascular compliance in the same subjects. The second study was a cross-sectional evaluation of 412 normotensive and hypertensive subjects conducted at the University of California San Diego. The second study (Mantel-Haenszel chi(2) test; P=0.05) showed that a greater proportion of black participants with poor blood pressure control had CYP3A5*1/*1 genotype. Evaluation of the untreated blood pressure from phase 1 of the first study showed that the blacks with CYP3A5*3/*3 (146+/-35 mm Hg) had a higher systolic blood pressure than those with the *1/*3 (119+/-14.1 mm Hg; P=0.0006) and *1/*1 (125+/-17.4 mm Hg; P=0.009) genotypes. For blacks in study 2, the CYP3A5*1 allele was more common in hypertensives (Fisher exact test; P=0.025) than normotensives. In whites there was no association between CYP3A5 genotype and blood pressure in either study. We conclude that although untreated blood pressure may be higher in blacks with the CYP3A5*3/*3 genotype, the CYP3A5*1 allele may be associated with hypertension that is more refractory to treatment in this ethnic group.
Ho
Herbert
H
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, 1001 W Tenth St, WD Myers Room W7123, Indianapolis, IN 46202, USA. heho@iupui.edu
Pinto
Amar
A
Hall
Stephen D
SD
Flockhart
David A
DA
Li
Lang
L
Skaar
Todd C
TC
Cadman
Peter
P
O'Connor
Daniel T
DT
Wagner
Urban
U
Fineberg
Naomi S
NS
Weinberger
Myron H
MH
D000483:Alleles; D000959:Antihypertensive Agents / Q000627:therapeutic use; D044383:Black People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D013599:Systole; D044465:White People / Q000235:genetics
D000959:Antihypertensive Agents; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A