Combined SSCP and heteroduplex analysis of the human plasma membrane Ca2+-ATPase isoform 1 in patients with essential hypertension

In recent theories concerning the pathogenesis of essential hypertension, a ltered calcium homeostasis plays an important role, Increased intracellular Ca2+ levels have repeatedly been reported in different cell types of hyper tensive subjects. In vascular smooth muscle cells the plasma membrane Ca2+- ATPase (PMCA) represents the most important Ca2+-ejection system, Modificat ions of this pump therefore have been assumed to increase contractile tone of small vessels. For this reason, the purpose of this study was to determi ne if genetic alterations in the hPMCA1 gene might be associated with arter ial hypertension. For detection of polymorphisms all 22 PMCA1 exons from 44 patients with essential hypertension (based on rigorous clinical data in a ddition to a positive family history) and from 40 normotensives without a f amily history of hypertension were PCR amplified and subsequently subjected to combined single-strand conformation polymorphism (SSCP) and heteroduple x (HTX) analysis. Despite the high sensitivity of almost 100%, differences could not be identified between hypertensives and normotensives within the two groups. These data indicate that at least in this population PMCA1 poly morphisms are presumably not related to common forms of essential hypertens ion. Furthermore, the high degree of evolutionary conservation of the PMCA1 gene underlines the pivotal role of this ATPase for cell physiology, (C) 1 999 Academic Press.