Hereditary Determinants of Human Hypertension Strategies in the Setting of Genetic Complexity

Essential hypertension is characterized by chronicallyelevated blood pressure with no specific underlying medical cause. Data on family history of affected individuals coupled with disease concordance rate in twins has estab-lished that both genetic and environmental factors determine susceptibility to hypertension. The heritability of hyperten-sion is often cited in the range of 30 % to 60%, with multiple contributory genes; additionally, ethnic and genetic heterogeneity participate in variable clinical presentation and drug response in hypertension, rendering genetic study of this disease a challenging task. Human population and animal studies have implicated several important etiologic pathways contributing to the clinical presentation of essential hyperten-sion that enable functional candidate gene association studies, in addition to more comprehensive genome wide linkage or association studies. Recent results also suggest a complex genetic architecture for hypertension and its associated risk traits, including evidence for pleiotropy (one gene3multiple traits), epistasis (gene-by-gene interaction), and on occasion molecular heterosis (a more extreme phenotype for heterozy-gotes than either homozygote class). Here we highlight recent findings on the genetics of hypertension that may lead to new approaches for investigating the pathogenesis, diagnosis, treatment, and prognosis of the disease