Association between the CYP3A5 genotype and blood pressure

被引:75
作者
Ho, H
Pinto, A
Hall, SD
Flockhart, DA
Li, L
Skaar, TC
Cadman, P
O'Connor, DT
Wagner, U
Fineberg, NS
Weinberger, MH
机构
[1] Indiana Univ, Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Dept Med, Div Biostat, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Indianapolis, IN 46202 USA
[4] Univ Calif San Diego, Sch Med, Dept Med, Div Nephrol, La Jolla, CA 92093 USA
关键词
cytochrome p450; blood pressure; genetics; polymorphism;
D O I
10.1161/01.HYP.0000151361.31736.96
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 approximate to 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.
引用
收藏
页码:294 / 298
页数:5
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