Association of CYP3A5 genotypes with blood pressure and renal function in African families.
OBJECTIVE
Renal cytochrome P450 3A5 (CYP3A5) activity has been associated with blood pressure and salt sensitivity in humans. We determined whether CYP3A5 polymorphisms are associated with ambulatory blood pressure (ABP) and with glomerular filtration rate (GFR) in African families.


METHODS
Using a cross-sectional design, 375 individuals from 72 families, each with at least two hypertensive siblings, were recruited through a hypertension register in the Seychelles (Indian Ocean). We analyzed the association between the CYP3A5 alleles (*1, *3, *6 and *7) and ABP, GFR and renal sodium handling (fractional excretion of lithium), from pedigree data, allowing for other covariates and familial correlations.


RESULTS
CYP3A5*1 carriers increased their daytime systolic and diastolic ABP with age (0.55 and 0.23 mmHg/year) more than non-carriers (0.21 and 0.04 mmHg/year). CYP3A5*1 had a significant main effect on daytime systolic/diastolic ABP [regression coefficient (SE): -29.6 (10.0)/-8.2 (4.1) mmHg, P = 0.003/0.045, respectively] and this effect was modified by age (CYP3A5*1 x age interactions, P = 0.017/0.018). For night-time ABP, the effect of CYP3A5*1 was modified by urinary sodium excretion, not by age. For renal function, CYP3A5*1 carriers had a 7.6(3.8) ml/min lower GFR (P = 0.045) than non-carriers. Proximal sodium reabsorption decreased with age in non-carriers, but not in CYP3A5*1 carriers (P for interaction = 0.02).


CONCLUSIONS
These data demonstrate that CYP3A5 polymorphisms are associated with ambulatory BP, CYP3A5*1 carriers showing a higher age- and sodium- related increase in ABP than non-carriers. The age effect may be due, in part, to the action of CYP3A5 on renal sodium handling.
Bochud
Murielle
M
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
Eap
Chin B
CB
Elston
Robert C
RC
Bovet
Pascal
P
Maillard
Marc
M
Schild
Laurent
L
Shamlaye
Conrad
C
Burnier
Michel
M
D000328:Adult; D000367:Age Factors; D000483:Alleles; D000704:Analysis of Variance; D044383:Black People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D018660:Blood Pressure Monitoring, Ambulatory; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005190:Family / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012964:Sodium / Q000378:metabolism; D018709:Statistics, Nonparametric
D003577:Cytochrome P-450 Enzyme System; D012964:Sodium; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A