Sodium-lithium countertransport kinetics were measured in 87 patients (50 male; 37 female) with heterozygous familial hypercholesterolaemia (FH) and a group of 38 age range and sex-distribution matched controls. Basic clinical data including basic anthropometry, blood pressure were obtained and blood was taken for detailed lipid biochemistry, glucose and insulin measurement. Patients with FH had elevated total cholesterol, low-density lipoprotein (LDL)-cholesterol and apolipoprotein B concentrations compared to controls. The activity and log transformed maximal velocity (Vmax) of the sodium-lithium countertransporter unlike the affinity (Km) were reduced in patients with FH compared to controls (geometric means 0.172 vs 0.217 mmol Li+/L.RBC.hr; P = 0.02; 0.237 vs0.317 mmol Li+/L.RBC.hr; P = 0.009 respectively). In multiple regression analysis, log normalised SLC activity correlated weakly with log triglyceride (β = 0.225; P = 0.06) and cholesterol (β = −0.112 P = 0.06). Log Vmaxcorrelated with log triglyceride (β = 0.307; P = 0.02), and high-density lipoprotein (HDL) (β = 0.74; P = 0.03) whilst Km correlated with HDL (β = 1.73; P < 0.001) and apoai (β = −1.76; P = 0.0048), LDL (β = −0.14; P = 0.05), and creatine kinase (β = 0.003; P = 0.01). Cholesterol and triglyceride concentrations rather than insulin resistance seem to be the key features affecting the environmental alteration of sodium lithium countertransporter Vmax in patients with familial hypercholesterolaemia.

BACKGROUNDAbnormal behaviour of the erythrocyte membrane sodium-lithium countertransporter (SLC) is associated with plasma triglyceride concentrations. Refsum's disease is characterized by progressive neurological dysfunction and accumulation of phytanic acid, an isoprenoid fatty acid, in fat-containing tissues.METHODSThis study explored the effects of plasma phytanic acid on SLC kinetics in nine Caucasian patients with Refsum's disease and in age- and sex-matched Caucasian control subjects.RESULTSA dose-dependent association was seen between countertransporter maximal velocity and phytanic acid content of low-density lipoprotein (LDL)-cholesterol (r = -0.61, r = -0.65 respectively; P = 0.05, P = 0.04) and high-density lipoprotein (HDL)-cholesterol (r = -0.81, -0.82 respectively; P = 0.005, P = 0.003). No significant association was seen with the sodium affinity of the transporter (r = -0.44, P = 0.20, for LDL; and -0.43, P = 0.21, for high-density lipoprotein).CONCLUSIONThese findings suggest that phytanic acid may alter the behaviour of the sodium-lithium countertransporter.

Sodium-lithium countertransport activity has been proposed as a marker for hypertension and is lower in black compared to Caucasian subjects both with and without vascular disease. The question arises of what is the primary kinetic locus of the altered behaviour of the countertransporter in black subjects and whether this is also seen in normotensive subjects from other non-Caucasian ethnic groups. We studied the sodium-lithium countertransporter in four ethnic groups (black [ n = 45], Caucasian [ n = 45], Chinese [ n = 40], and South Asian [ n = 39]) of age-matched normotensive males (age range 18–35 y) with no first-degree family history of hypertension or diabetes. The clinical and laboratory characteristics of the subjects were similar in all four ethnic groups. Minor differences noted were: significantly higher mean height, weight and serum creatinine concentration ( P < 0.001) and significantly lower plasma triglyceride concentration ( P = 0.02) in the black compared to the other study groups. Sodium-lithium countertransport activity (mmol Li/l RBC h) was significantly lower in the black subjects (0.113 [0.013–0.265]) compared with the other groups (Caucasian, 0.247 [0.037–0.614]; Chinese, 0.210 [0.100–0.707]; South Asian, 0.211 [0.037–0.617]; P < 0.001). no differences were noted between the four study groups in respect of k Na . Mean (s.d.) V max values (mmol Li/l RBC h) were also reduced in the black subjects (0.152 [0.088]) compared to the other ethnic groups (Caucasian, 0.376 [0.159]; Chinese, 0.364 [0.182]; South Asian, 0.329 [0.155]; P < 0.001) and there was a strong relationship between countertransport activity and v max ( r > 0.52; P < 0.001; for each of the study groups). the differences in mean v max noted between the Caucasian, South Asian and Chinese subjects were not significant.These results show that, when compared with three other selected ethnic groups, black subjects demonstrate an altered behaviour with respect to V max of the sodium-lithium countertransporter, which occurs in the absence of demonstrable vascular pathology.