Sodium excretion as a modulator of genetic influence on arterial stiffness and other cardiovascular phenotypes

Hypertension is a chronic age-related disorder, affecting nearly 20% of all adult Europeans. This disease entails debilitating cardiovascular complications and is the leading cause for drug prescriptions in Europeans older than 50 years. Intensive research over the past two decades has so far failed to identify common genetic polymorphisms with a major impact on blood pressure or associated cardiovascular phenotypes, suggesting that multiple genes each with a minor impact, along with gene–gene and gene–environment interactions, play a role. The European Project on Genes in Hypertension (EPOGH) is a large-scale, family-based study in which participants from seven different populations were phenotyped and genotyped according to standardized procedures. The EPOGH demonstrated that phenotype–genotype relations strongly depend on host factors such as gender and lifestyle, in particular salt intake as reflected by the 24-h urinary excretion of sodium. Individuals with the same genetic predisposition had different vascular stiffness, left ventricular mass or heart rate variability, depending on whether they ate a high-sodium or a low-sodium diet. The EPOGH therefore highlights the concept that phenotype–genotype relations can only be studied within a defined ecogenetic context.