Macro- and Microelement Status in Animal and Human Hypertension: the Role of the ACE Gene I/D Polymorphism

Abstract

Genetic factors that predispose to hypertension may contribute to element disturbances observed in hypertensive patients. We tested the hypothesis that the deletion allele of the angiotensin-converting enzyme (ACE) gene is associated with element imbalances in hypertension. The concentrations of elements in genetically predisposed to hypertension rats (SHRs) and their controls (WKY rats) were also examined. ICP-MS was used for elemental analysis of human hair and animal fur. Genotyping was performed by PCR. We also measured micronuclei frequency and distribution of peripheral blood leukocytes in cell cycle phases by flow cytometry and studied the correlations of these parameters with element contents. In general, the tendency for higher levels of toxic and lower levels of essential elements is observed in hypertension, specifically in patients carrying the D allele. Hypertensive men had significantly higher Be, V, Cr, As, Mo, Ag, Sb, and Na levels and lower Ca, Zn, Ba, and U levels compared with control subjects; the differences were not significant for Mg, Al, K, Mn, Fe, Co, Ni, Cu, Se, Cd, Tl, Pb, and Th. The D allele was associated with higher Be, Mo, and Th levels and lower Zn, Se, and Tl levels. The concentrations of Ca, Co, Mo and U were higher in SHR than those in the WKY rats. Mo, an antagonist of Cu, positively correlated with the S-phase cells, and Cu positively correlated with micronuclei frequency. The results suggest an involvement of the ACE I/D polymorphism in element imbalances in hypertension and attract attention to the possible significant role of genetic factors in Mo accumulation.

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