1. CYP3A5 GENOTYPE AFFECTS SYSTOLIC BLOOD PRESSURE IN THE GENERAL POPULATION Mike Zuurman 1, Reinhold Kreutz 2, Silke Kain 3, Paul De Jong 1, Gerjan Navis 1. Introduction The cytochrome-P450 3A5 (CYP3A5) enzyme is expressed in the kidney and has been implicated as a second enzyme protecting mineralocorticoid receptor (MR) from glucocorticoid occupancy. Thus, CYP3A5 could mediate a blood pressure (BP) lowering effect. A recent study showed that expression of CYP3A5 in the kidney was determined by the A6986G polymorphism in CYP3A5. Thus, appreciable expression was only found in carriers of the CYP3A5*1 allele but not in carriers of the CYP3A5*3 allele. Goal We investigated the association and putative interaction between CYP3A5 genotype, BP and 24 hours sodium excretion (UNa + V) in the general population. Methods -Study population: The general population-based PREVEND cohort -Subject selection: Caucasian, non-diabetic, no renal disease-related proteinuria, not using antihypertensive medication, genotyped for CYP3A5 *1*3 (n=6766) -Where appropriate *1/*1 and *1/*3 individuals were clustered -Linear regression models included genotype, age, gender, body mass index, smoking status and urinary sodium excretion (“fully adjusted”) Results: Table 1 Presented are arithmetic means (standard deviation) or percentages. Pearson Chi-square test or ANOVA did not show significant differences in subjects characteristics. Odds ratios for hypertension (B) and their significance (P) were calculated for Presence of *1 allele versus *3/*3 homozygotes using a binary logistic model with age and genotype, OR(age); with age, body mass index, smoking, UNaV + and genotype, OR(full); or no other covariates, OR. B indicates the linear regression coefficient of the *3/*3 genotype vs *1/*1 + *1/*3 in mmHg, p indicates the significance of the contribution of the genotype to the model. Arithmetic means of the values as predicted by each model are shown with their standard deviations. n=6140. A BC Mean measured systolic, diastolic blood pressure and pulse pressure by quartiles of UNa + V (mmol/24) by genotype (*1/*1 +*1/*3, solid circles, vs *3/*3, open circles), A, B and C. Linear regression models predicted influence (p=0.034) of genotype on the parabolic relationship between UNa + V and systolic blood pressure, although the interaction did not improve the model compared to a model without UNa + V*Genotype interaction variables (change of the F square statistic was not significant with a p-value of 0.133). n=6140. Results: Figure 1 1. Internal Medicine/Div. Nephrology, UMCG, Groningen, Netherlands 2. Clinical Pharmacology, Campus Benjamin Franklin, Charite - University Medicine, Berlin, Germany 3. Nephrology, Campus Virchow Klinikum, Charite - University Medicine, Berlin, Germany Conclusions -SBP and PP in the general population is associated with CYP3A5 *1/*3 genotype -SBP and PP in *1 allele-carriers is significantly lower compared to *3/*3 homozygotes -SBP and UNa + V show a parabolic relation that is altered by CYP3A5 *1/*3 genotype -The parabolic relationship, SBP vs UNa + V, did not improve the model for SBP or PP. Results: Table 2