A prospective study of sodium-lithium countertransport and hypertension in Utah.

Abstract

A 7-year prospective study of a cohort of 1,458 normotensive adults from Utah pedigrees, screened from 1980 to 1985, was done to determine whether baseline levels of sodium-lithium countertransport were associated with an increased risk of future hypertension. Subsequent new hypertension (n = 39) was ascertained in 1989 from detailed follow-up medical questionnaires (67% response). Previous segregation analyses on a subset of these pedigree members who responded (n = 342) using family relationships in addition to countertransport levels have shown statistically inferred major gene segregation of sodium-lithium countertransport levels. In the normotensive adults inferred by segregation analysis to carry the recessive major gene for high sodium-lithium countertransport, new-onset hypertension occurred in 18.8% (3 of 16) compared with 3.7% (12 of 326) in the low sodium-lithium countertransport genotype group (relative risk, 4.6 [1.6, 13.9]; p = 0.03). However, an elevated baseline sodium-lithium countertransport level without genotype information from segregation analysis did not increase the risk of future hypertension in the complete cohort of adult pedigree members (relative risk, 1.02 [0.85, 1.22]). Adjustment for other risk factors reduced the relative risk to 0.90 (0.72, 1.11). We conclude that the presence of a major gene for sodium-lithium countertransport or another closely linked gene, rather than the actual level of sodium-lithium countertransport, may increase the risk of hypertension onset. High sodium-lithium countertransport levels do not increase the risk of future hypertension for individuals in whom only polygenic and environmental effects determine sodium-lithium countertransport level.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin sensitivity, sodium-lithium countertransport and platelet free calcium concentrations in normotensive men with a family history of hypertension

“…8 Recently, however, there has been some controversy concerning the appropriateness of the method for determining the V max of NaLiCT across the red cell membrane. The method is based on the assumption that concentrations of external sodium approaching physiological levels are sufficient to saturate the external sodium binding sites, resulting in the transporter achieving its maximal turnover rate.…”

“…[3][4][5][6] An increase in erythrocyte sodium-lithium countertransport (NaLiCT) activity is one of the most consistent alterations in membrane ion transport that have been demonstrated in essential hypertension. [7][8][9][10][11] Recently it was also shown that increased NaLiCT activity might be a predictor of subsequent hypertension. 12,13 It has also been suggested that increased NaLiCT activity might be a marker of genetic predisposition to hypertension, since NaLiCT activity has been reported to be increased in normotensive relatives of hypertensive individuals.…”

Sodium-lithium countertransport activity in normotensive offspring of hypertensive black Africans

“…13 This familial nature is thought to be due to genetic factors as many studies, including that of identical twins, show that SLC activity is genetically inherited. 9,10,15 The level of lithium efflux was similar in the normotensive offspring of hypertensive parents to that of the already hypertensive group. However, it is worthy of note, that the level of intra-erythrocytic sodium was not elevated in the normotensive offspring of hypertensive parents over that of normotensive offspring of normotensive parents, unlike the case in hypertensive patients.…”

“…[3][4][5][6][7][8] There is now a body of evidence suggesting that sodium-lithium countertransport (SLC) abnormality in erythrocytes is associated with hypertension, as well as a predisposition to its development in Caucasians, 5,[9][10][11][12] that it aggregates in families 9,13,14 and that it is strongly influenced by genetic factors. 9,[13][14][15] Racial differences have been described in erythrocyte cation transport and it is thought that these changes are either reduced or may not occur in nonwhite persons, especially blacks. [16][17][18] However, Oforofuo et al 19 described an increased activity in a small group of Nigerian hypertensive patients but did not exclude the effects of drugs and also did not investigate the normotensive offspring of hypertensive patients.…”

Lipid lowering: another method of reducing blood pressure?

“…17 In the Utah study, which included patients with familial combined hyperlipidaemia (FCH) and familial hypercholesterolaemia (FH), SLC activity also correlated strongly with blood pressure and lipids. 18,19 Both these epidemiological studies linked SLC to triglycerides, insulin resistance, and lipoprotein lipase activity as have studies in patients with type V hyperlipidaemia. 20 The Utah study population defined a subgroup of up to 10% of patients with essential hypertension who had a phenotype of dyslipidaemia allied with hypertension with a strong genetic component.…”