Hypertension and the Genetics of Red Cell Membrane Abnormalities

Altered erythrocyte membrane protein composition mirrors pleiotropic effects of hypertension susceptibility genes and disease pathogenesis

“…Functional alterations in Na þ -Li þ countertransport and other membrane ion transporters are thought to be responsible for abnormal intracellular distribution of calcium ions required for contraction of smooth muscle cells, leading to increased cytosolic free calcium and arterial contractility leading to hypertension [12,22,23]. These observations made erythrocytes an attractable and biologically plausible model for studying the role of membrane alterations in the molecular mechanisms of hypertension [12,14,24,25].…”

“…Lastly, an alteration in the protein composition of the membrane cytoskeleton has the ability to influence the functioning of the ion transport ATPases of the membrane through conformational modifications of their active centers [58,66,67]. Animal studies showed that a removal of spectrin from erythrocytes results in two and three-fold decreasing in the activity of Na þ K -ATPase and Ca 2þ -ATPase, respectively [66,68], pointing out that reduced levels of spectrins has the potential to influence the activity of transport ATPases, a possible mechanism involved into the ion transport abnormalities in human hypertension [13,23,24]. The present study revealed that the proteins directly involved in glucose metabolism such as GLUT and glycolytic enzyme GAPDH were also significantly altered in hypertensive patients compared with healthy subjects.…”

“…The altered activity of monovalent ion transporters in essential hypertension, in contrast to monogenic hypertensions, may be because of abnormalities of systems involved in the regulation of their expression and/or function [23]. Familial aggregation and higher concordance of increased Na þ -Li þ countertransport in monozygotic twins than in dizygotic twins suggest multifactorial nature of membrane disorders in essential hypertension [24]. This means that the ion transport abnormalities of cell membrane in essential hypertension are attributable to the effects of multiple genes, which have the potential to modify expression of genes whose products form the structure of the cell membrane.…”

Evidence for single gene contributions to hypertension and lipid disturbances: definition, genetics, and clinical significance

“…It correlates much better in MZ twins than in DZ twins, and significantly better in siblings than in spouses (Dadone et al 1984). Complex segregation analysis (Dadone et al 1984, Boerwinkle et al 1984, Motulsky et al 1987, Hasstedt et al 1988) has identified a recessively segregating trait for high levels of SLC present in approximately 5% of the general population. It is associated with twice normal levels of SLC and approximately four-fold increase in hypertension in a 7-year prospective study (Hunt et al 1991).…”

“…Three rows in this diagram indicate three major groups of syndromes including overproduction of adrenal steroid hormones, disturbances in fluid and electrolyte balance, and metabolic abnormalities involving dyslipidemia, hyperinsulinemia and obesity. Table 1 summarizes some of the most prominent examples of segregating traits thought to be related to the occurrence of hypertension (Williams et al 1983, Dadone et al 1984, Boerwinkle et al 1984, Motulsky et al 1987, Hasstedt et al 1988, Hunt et al 1991, Dadone et al 1986, Berry et al 1989, Hunt et al 1993, Elbein et al 1991, Schumacher et al 1992a,b, Hasstedt et al 1989, Austin et al 1988. Most of them have quite high estimates of heritability (proportion of total variance attributable to genetic factors).…”