Effects of lipids in patients with familial hypercholesterolaemia on the kinetics of the sodium-lithium countertransporter.
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 vs. 0.317 mmol Li+/L.RBC.hr; P = 0.009 respectively). In multiple regression analysis, log normalised SLC activity correlated weakly with log triglyceride (beta = 0.225; P = 0.06) and cholesterol (beta = -0.112 P = 0.06). Log Vmax correlated with log triglyceride (beta = 0.307; P = 0.02), and high-density lipoprotein (HDL) (beta = 0.74; P = 0.03) whilst Km correlated with HDL (beta = 1.73; P<0.001) and apoAI (beta = -1.76; P = 0.0048), LDL (beta = -0.14; P = 0.05), and creatine kinase (beta = 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.
Wierzbicki
A S
AS
Department of Chemical Pathology, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK. Anthony.Wierzbicki@kcl.ac.uk
Hardman
T C
TC
Cheung
J
J
Lambert-Hammill
M
M
Patel
S
S
Morrish
Z
Z
Lumb
P J
PJ
Lant
A F
AF
D000328:Adult; D017920:Antiporters / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D007700:Kinetics; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D017920:Antiporters; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides; C045885:sodium-lithium countertransporter; D002784:Cholesterol