GENETIC POLYMORPHISMS AND ERYTHROCYTE SODIUM-LITHIUM COUNTERTRANSPORTIN ESSENTIAL-HYPERTENSION

Erythrocyte sodium-lithium countertransport (SLC) activity is elevated in essential arterial hypertension. With the growing attention to the genetic substrate of disturbed biochemical tests associated with esse ntial arterial hypertension, we were particularly interested in the in volvement of key genes for the regulation of SLC, possibly related to the pathophysiology of essential arterial hypertension. Consequently, the aim of the present study was to investigate SLC and its determinin g factors in essential hypertension. The influence of haptoglobin (Hp) -polymorphism, insertion/deletion polymorphism of angiotensin converti ng enzyme (ACE-I/D) and MNS blood group system on the regulation of SL C was studied. SLC activity was studied in a cross-sectional case-cont rol study including 90 Caucasians: 60 patients with essential arterial hypertension who had been treated for at least 1 year and 30 normoten sive controls. In essential hypertension, the SLC activity is signific antly higher (P = 0.00005) than in controls. In normotensive patients, no differences in SLC are observed for the different polymorphisms st udied. However, in the hypertensive group, SLC activity is higher (P = 0.003) in Hp 2-1 phenotype and independent of ACE-I/D genotyping and MNS blood group polymorphism. Multifactor analysis of variance in esse ntial hypertension reveals significant (P = 0.001) differences in SLC activity for the presence or absence of Hp 2-1 phenotype and for body weight (P = 0.0003). Multivariate regression analysis shows the same p arameters to be independent determining factors of SLC in essential ar terial hypertension. No relation is found between SLC activity and tar get organ damage which includes coronary artery disease, peripheral ar terial occlusive disease, left ventricular hypertrophy and cerebrovasc ular accident. We conclude that erythrocyte SLC activity is elevated d espite pressure-lowering therapy. In essential arterial hypertension, individuals of Wp 2-1 phenotype show higher SLC activity than patients of other Hp-types, suggesting genetic heterogeneity of essential arte rial hypertension. The presence or absence of Hp 2-1 phenotype is an i ndependent determining factor of SLC activity whereas body weight code termines SLC activity in essential hypertension.