With governmental authorities, academicians, healthcare providers and industry grappling with the level of salt in the diet in an effort to reduce its impact on high blood pressure, new data evaluating a potential genetic component to salt-sensitive hypertension will be presented at the American Society of Hypertension, Inc.'s 25th Annual Scientific Meeting and Exposition (ASH 2010).
Essential hypertension is a complex condition caused by the interaction of multiple genetic and environmental factors, including salt intake. Salt-inducible kinase 1 (SIK1), a kinase from the 5' AMP-activated protein kinase family, is part of a cell network involved in controlling active sodium transport during small increases in intracellular sodium.
In this study of 22,416 subjects (20,784 Caucasians; 1,632 Asians), investigators found that a polymorphism in the human SIK1 gene that resulted in a mutation within the SIK1 protein, is associated with variations in blood pressure. The presence of the minor allele of this polymorphism was associated with elevated blood pressure in Asians but was protective in Caucasians. In Caucasians, it is the major allele that associated with elevated blood pressure and with increased left ventricular mass. SIK1 was observed to be present in kidney cells, vascular smooth muscle cells and endothelial cells. Functional studies in cell culture demonstrated that the polymorphism influences active sodium transport in vascular smooth muscle cells, and in renal cells under basal and sodium stress conditions, as well as in response to aldosterone.
"All this evidence suggests that SIK1 may represent an important regulator of sodium transport in response to salt intake in the kidney and vasculature, and that modulation of its activity may have a significant impact in the development of high blood pressure and/or cardiac complications," said study author Alejandro M. Bertorello, M.D., Ph.D., associate professor, head of Membrane Signaling Networks, at the Department of Medicine, Atherosclerosis Research Unit, Karolinska Institutet, Karolinska University Hospital-Solna Stockholm, Sweden. "Clearly much additional research is needed, but we're excited that these data provide additional evidence supporting this potential new target for blood pressure treatment."