The molecular basis of hypertension.
Hypertension is a substantial public health problem affecting about 25% of the population in industrialized societies. The disorder is responsible for many common causes of morbidity and mortality. Despite the important role of hypertension as a cause of disease, its pathogenesis remains largely unknown. The application of genetic approaches to rare monogenic (Mendelian) forms of hypertension and hypotension has begun to delineate molecular pathways underlying human blood pressure variation, defining disease pathogenesis and identifying targets for therapeutic intervention. In all cases the pathophysiology is altered net renal salt reabsorption. Mutations are either affecting circulating mineralocorticoid hormones or renal ion channels and transporters. Examples are glucocorticoid-remediable aldosteronism (GRA), Liddle's syndrome, the syndrome of hypertension exacerbated in pregnancy, and apparent mineralocorticoid-excess (AME). Recently, alterations in genes of a novel serine-threonine kinase family (WNK1 and WNK4) were identified causing pseudohypoaldosteronism type II. The molecular pathway of this syndrome remains unclear. Additionally, there is the syndrome of hypertension associated with brachydactyly type E (Bilginturan's syndrome), for which the molecular mechanism has yet to be identified.
Toka
Hakan R
HR
Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
D000450:Aldosterone / Q000097:blood; D053503:Epithelial Sodium Channels; D005260:Female; D005385:Fingers / Q000002:abnormalities; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D020125:Mutation, Missense; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology; D011546:Pseudohypoaldosteronism / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D013577:Syndrome
D053503:Epithelial Sodium Channels; D018161:Receptors, Mineralocorticoid; D015222:Sodium Channels; D000450:Aldosterone