Aldosterone increases plasma volume and may be involved with resistant hypertension. P-glycoprotein is a transporter involved in the distribution and disposition of aldosterone, and is encoded by the MDR-1 gene. MDR-1 has functional polymorphisms that may affect P-glycoprotein expression. We hypothesized that the C3435T polymorphism in MDR-1 could be associated with resistant hypertension and with changes in hypertension-related parameters. We studied 105 healthy volunteers, 137 hypertensive patients responsive to treatment, and 83 resistant hypertensive patients. While we found no association of C3435T genotypes with resistance to treatment (p = 0.31), C allele was associated with hypertension (p = 0.03). Furthermore, the CC genotype was associated with higher systolic blood pressure (p < 0.01 for both daytime and nighttime, respectively) and diastolic blood pressure (p < 0.01 for both daytime and nighttime, respectively). This effect was probably independent of aldosterone, as we found no differences in aldosterone plasma levels, nor in pulse wave velocity (PVW) between the genotypes groups (p = 0.77 and p = 0.48, respectively). Our results show an association of C3435T with hypertension and with blood pressure levels in resistant hypertensive subjects. © 2014 The Author(s).152170176Cutler, J.A., High blood pressure and end-organ damage (1996) J Hypertens Suppl, 14, pp. S3-S6De Souza, W.A., Sabha, M., De Faveri, Favero, F., Intensive monitoring of adherence to treatment helps to identify "true" resistant hypertension (2009) J Clin Hypertens (Greenwich), 11, pp. 183-191Calhoun, D.A., Jones, D., Textor, S., Resistant hypertension: Diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research (2008) Hypertension, 51, pp. 1403-1419Chobanian, A.V., Bakris, G.L., Black, H.R., The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report (2003) JAMA, 289, pp. 2560-2572Calhoun, D.A., Jones, D., Textor, S., Resistant hypertension: Diagnosis, evaluation, and treatment: A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research (2008) Circulation, 117, pp. e510-e526Cuspidi, C., Vaccarella, A., Negri, F., Resistant hypertension and left ventricular hypertrophy: An overview (2011) J Am Soc Hypertens, 4, pp. 319-324Gaddam, K.K., Nishizaka, M.K., Pratt-Ubunama, M.N., Characterization of resistant hypertension: Association between resistant hypertension, aldosterone, and persistent intravascular volume expansion (2008) Arch Intern Med, 168, pp. 1159-1164Pimenta, E., Gaddam, K.K., Oparil, S., Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: Results from a randomized trial (2009) Hypertension, 54, pp. 475-481Struthers, A.D., MacDonald, T.M., Review of aldosterone- and angiotensin II-induced target organ damage and prevention (2004) Cardiovasc Res, 61, pp. 663-670Pitt, B., Remme, W., Zannad, F., Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction (2003) N Engl J Med, 348, pp. 1309-1321Pitt, B., Zannad, F., Remme, W.J., The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators (1999) N Engl J Med, 341, pp. 709-717Engbaek, M., Hjerrild, M., Hallas, J., The effect of low-dose spironolactone on resistant hypertension (2010) J Am Soc Hypertens, 4, pp. 290-294Ueda, K., Okamura, N., Hirai, M., Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone (1992) J Biol Chem, 267, pp. 24248-24252Uhr, M., Holsboer, F., Muller, M.B., Penetration of endogenous steroid hormones corticosterone, cortisol, aldosterone and progesterone into the brain is enhanced in mice deficient for both mdr1a and mdr1b P-glycoproteins (2002) J Neuroendocrinol, 14, pp. 753-759Bello-Reuss, E., Ernest, S., Holland, O.B., Role of multidrug resistance P-glycoprotein in the secretion of aldosterone by human adrenal NCI-H295 cells (2000) Am J Physiol Cell Physiol, 278, pp. C1256-C1265Fojo, A.T., Ueda, K., Slamon, D.J., Expression of a multidrug-resistance gene in human tumors and tissues (1987) Proc Natl Acad Sci U S A, 84, pp. 265-269Meissner, K., Sperker, B., Karsten, C., Expression and localization of P-glycoprotein in human heart: Effects of cardiomyopathy (2002) J Histochem Cytochem, 50, pp. 1351-1356Thiebaut, F., Tsuruo, T., Hamada, H., Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues (1987) Proc Natl Acad Sci U S A, 84, pp. 7735-7738Parker, R.B., Yates, C.R., Laizure, S.C., P-glycoprotein modulates aldosterone plasma disposition and tissue uptake (2006) J Cardiovasc Pharmacol, 47, pp. 55-59Hoffmeyer, S., Burk, O., Von Richter, O., Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo (2000) Proc Natl Acad Sci U S A, 97, pp. 3473-3478Kimchi-Sarfaty, C., Oh, J.M., Kim, I.W., A "silent" polymorphism in the MDR1 gene changes substrate specificity (2007) Science, 315, pp. 525-528Meissner, K., Jedlitschky, G., Zu, M., Schwabedissen, H., Modulation of multidrug resistance P-glycoprotein 1 (ABCB1) expression in human heart by hereditary polymorphisms (2004) Pharmacogenetics, 14, pp. 381-385Wang, D., Johnson, A.D., Papp, A.C., Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C>T affects mRNA stability (2005) Pharmacogenet Genomics, 15, pp. 693-704Sissung, T.M., Gardner, E.R., Piekarz, R.L., Impact of ABCB1 allelic variants on QTc interval prolongation (2011) Clin Cancer Res, 17, pp. 937-946Bochud, M., Eap, C.B., Maillard, M., Association of ABCB1 genetic variants with renal function in Africans and in Caucasians (2008) BMC Med Genomics, 1, p. 21Cascorbi, I., Paul, M., Kroemer, H.K., Pharmacogenomics of heart failure - Focus on drug disposition and action (2004) Cardiovasc Res, 64, pp. 32-39Eap, C.B., Bochud, M., Elston, R.C., CYP3A5 and ABCB1 genes influence blood pressure and response to treatment, and their effect is modified by salt (2007) Hypertension, 49, pp. 1007-1014VI Brazilian Guidelines on Hypertension [in Portuguese] (2010) Arq Bras Cardiol, 95, pp. 1-51Taylor, D.W., Sackett, D.L., Haynes, R.B., Compliance with antihypertensive drug therapy (1978) Ann N y Acad Sci, 304, pp. 390-403Morisky, D.E., Green, L.W., Levine, D.M., Concurrent and predictive validity of a self-reported measure of medication adherence (1986) Med Care, 24, pp. 67-74De Souza, W.A., Yugar-Toledo, J.C., Bergsten-Mendes, G., Effect of pharmaceutical care on blood pressure control and health-related quality of life in patients with resistant hypertension (2007) Am J Health Syst Pharm, 64, pp. 1955-1961Zolk, O., Jacobi, J., Pahl, A., MDR1 genotype-dependent regulation of the aldosterone system in humans (2007) Pharmacogenet Genomics, 17, pp. 137-144Manunta, P., Ferrandi, M., Bianchi, G., Endogenous ouabain in cardiovascular function and disease (2009) J Hypertens, 27, pp. 9-18Tripodi, G., Citterio, L., Kouznetsova, T., Steroid biosynthesis and renal excretion in human essential hypertension: Association with blood pressure and endogenous ouabain (2009) Am J Hypertens, 22, pp. 357-363Fromm, M.F., Importance of P-glycoprotein at blood-tissue barriers (2004) Trends Pharmacol Sci, 25, pp. 423-429