The apolipoprotein E2 allele modulates activity and maximal velocity of the sodium-lithium countertransporter.
BACKGROUND
Alterations in erythrocyte sodium-lithium countertransport (SLC) activity and its maximal velocity (Vmax) are associated with hypertension and hypertriglyceridemia. The presence of apolipoprotein (apo) E variants is associated with hypertriglyceridemia. This study investigated the relationship between apoE phenotype and SLC kinetics.


METHODS
Cardiovascular risk factors and SLC kinetics were measured in 171 subjects and 69 controls. Apolipoprotein E phenotypes were determined by Western blotting.


RESULTS
Patients were 51% male, aged 56+/-13 years, with a blood pressure (BP) of 134+/-22/81+/-11 mm Hg, total cholesterol of 6.71+/-1.57 (256+/-61 mg/dL); median triglycerides 1.65 mmol/L (146 mg/dL) (range, 0.31 to 9.85 mmol/L; 27 to 872 mg/dL) and high-density lipoprotein (HDL) 1.39+/-0.43 mmol/L (54+/-16.6 mg/dL); fasting glucose 4.91+/-0.61 mmol/L (88.5+/-11.0 mg/dL); median insulin 11.7 IU/L (range, 3.7 to 39.8 IU/L). Phenotype frequencies were E3/E3 56%, E2/E3 14%, E2/E2 1%, E3/E4 27%, and E4/E4 2%. The SLC activity, Vmax, and sodium affinity (Km) were not significantly different with respect to apoE phenotype in simple analysis by Kruskal Wallis test. However, in multiple regression analysis after exclusion of BP, a strong co-correlate of SLC activity, the presence of an apoE2 allele was associated reduced activity (beta = -0.061; P = .01) along with HDL:apoA1 ratio (beta = -0.170; P < .001), whereas for the kinetic parameter Vmax, associations were found with triglyceride (beta = 0.029; P = .04), HDL:apoA1 ratio (beta = -0.186; P = .03) and the presence of an apoE2 allele (beta = -0.089; P = .04).


CONCLUSIONS
These findings suggest that the apoE phenotype may modulate SLC activity and that the presence of an apoE2 allele phenotype is associated with lower SLC activity and Vmax.
Wierzbicki
Anthony S
AS
Department of Chemical Pathology, St Thomas' Hospital, London, United Kingdom. anthony.wierzbicki@kcl.ac.uk
Hardman
Timothy C
TC
Cheung
Joseph
J
Lambert-Hammill
Michelle
M
Patel
Surinda
S
Morrish
Zoe
Z
Lumb
Peter J
PJ
Lant
Ariel F
AF
D000328:Adult; D000368:Aged; D000483:Alleles; D017920:Antiporters / Q000378:metabolism*; D053329:Apolipoprotein E2; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors
D017920:Antiporters; D053329:Apolipoprotein E2; D001057:Apolipoproteins E; C045885:sodium-lithium countertransporter