477 ISSN 1462-2416 10.2217/14622416.10.3.477 © 2009 Future Medicine Ltd Pharmacogenomics (2009) 10 (3), 477–487 Review CYP3A5 and ABCB1 genes and hypertension Hypertension is one of the leading causes of dis- ease burden worldwide [1] . Hypertension affects approximately 37–55% of the adult population in Europe [2,3] . Hypertension prevalence is even higher in Africa and Asia [4,5] , is a major car- diovascular risk factor for stroke [6] , coronary artery disease [7,8] , heart failure [9] and end-stage renal disease [10,11] , and it also increases all-cause mortality [12] . Currently, less than one third of hypertensives are treated and controlled (using the 140/90 mmHg threshold) [2] . The prevalence of hypertension is increasing in adolescents and children in some, but not all, countries [13,14] , which may lead to early development of cardio- vascular outcomes. These observations illustrate the high burden of hypertension in the general population across all age groups. Although various lifestyle and dietary fac- tors are associated with hypertension, specific biological determinants of primary or essential hypertension (as opposed to secondary forms of hypertension), which represents 95% of the hypertensive population, are still poorly under- stood. There is evidence that hypertension aggregates in families. In nontwin studies, her- itability of systolic blood pressure and diastolic blood pressure ranged from 0 to 0.68 and from 0.21 to 0.58, respectively [15–22] , which suggests that genetic determinants play a role in hyper- tension and blood pressure control. Although the main antihypertensive drugs effectively and substantially lower blood pressure [23] , there is a marked variability in the individual response to these drugs [24] . Better knowledge of the genetic basis of blood pressure control may change the management of hypertension by replacing the current largely empirical therapy by more effec- tive, targeted treatments tailored to the genetic characteristics of the patient and their response to specific medications [25] . For such a widely prevalent disease as essential hypertension, even modest improvements in the clinical man- agement of hypertensive patients can have an important impact at the population level. The identification of genetic variants involved in blood pressure control has been very difficult so far [26] . One of the major reasons explaining this difficulty may be that blood pressure regula- tion results from the interactions of many genes and environmental factors, so that each gene is likely to only have a small effect on blood pres- sure [27] . Recent data in animal models of hyper- tension reinforce the multifactorial and complex nature of hypertension and underline the impor- tance of looking for biologic gene–gene interac- tions [28–31] . Although our current knowledge of the physiology of hypertension suggests that interactions between genetic determinants are likely to be the norm rather than the excep- tion [32] , a lot of research conducted in the field does not account for this complexity. Reasons include insufficient sample size (assessing inter- actions requires large samples) and complex- ity of the statistical analyses [32] . A new gene- centric 50K microarray chip (IBC chip) has now been designed (Illumina, CA, USA) and targets approximately 2100 genes involved in cardiovascular disease, including hypertension Hypertension is the first single modifiable cause of disease burden worldwide. Genes encoding proteins that are involved in the metabolism (CYP3A5 ) and transport ( ABCB1) of drugs and hormones might contribute to blood pressure control in humans. Indeed, recent data have suggested that CYP3A5 and ABCB1 gene polymorphisms are associated with blood pressure in the rat as well as in humans. Interestingly, the effects of these genes on blood pressure appear to be modified by dietary salt intake. This review summarizes what is known regarding the relationships of the ABCB1 and CYP3A5 genes with blood pressure, and discusses the potential underlying mechanisms of the association. If the role of these genes in blood pressure control is confirmed in other populations and other ethnic groups, these findings would point toward a new pathway for blood pressure control in humans. KEYWORDS: ABCB1 n blood pressure n CYP3A5 n dietary salt intake n gene–gene interaction n hypertension n renin–angiotensin system Murielle Bochud 1† , Pascal Bovet 1 , Michel Burnier 2 & Chin B Eap 3,4 † Author for correspondence: 1 Insitute of Social and Prevenive Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) et Université de Lausanne, Rue du Bugnon 17, CH-1005 Lausanne, Switzerland Tel.: +41 213 140 899; Fax: +41 213 147 373; Murielle.Bochud@chuv.ch 2 Service de Néphrologie, Centre Hospitalier Universitaire Vaudois (CHUV), Université de Lausanne, Switzerland 3 Unité de Biochimie et Psychopharmacologie Clinique, Centre des Neurosciences Psychiatriques, Université de Lausanne, Hôpital de Cery, Switzerland 4 Ecole de Pharmacie, Université de Genève, Université de Lausanne, Switzerland For reprint orders, please contact: reprints@futuremedicine.com