Context-Dependency of Relations Between Cardiovascular Phenotypes and Genes Involved in Sodium Homeostasis: Findings from the European Project on Genes in Hypertension

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 then 50 years. Intensive research over the past two decades failed so far to identify common genetic polymorphisms with 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 7 different populations were phenotyped and genotyped according to standardised procedures. This review article summarizes the initial 5-year findings and puts these observations into perspective against other published studies. 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-hour urinary excretion of sodium. EPOGH therefore highlights the concept that phenotype-genotype relations can only be studied within a defined ecogenetic context.