The apolipoprotein E2 allele modulates activity and maximal velocity of the sodium–lithium countertransporter

• Published in: American journal of hypertension Vol. 15; no. 7; pp. 633 - 637
• Main Authors: Wierzbicki, Anthony S, Hardman, Timothy C, Cheung, Joseph, Lambert-Hammill, Michelle, Patel, Surinda, Morrish, Zoe, Lumb, Peter J, Lant, Ariel F
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2002; Oxford University Press; Elsevier Science
• Subjects: Adult; Aged; Alleles; Antiporters - metabolism; apolipoprotein E; Apolipoprotein E2; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Cohort Studies; Female; Humans; hyperlipidemia; Hypertension - epidemiology; Hypertension - genetics; Hypertension - metabolism; Hypertriglyceridemia - epidemiology; Hypertriglyceridemia - genetics; Hypertriglyceridemia - metabolism; Male; Medical sciences; Middle Aged; Phenotype; polymorphism; Polymorphism, Genetic; Risk Factors; Sodium–lithium countertransport; triglyceride; triglyceride; Sodium–lithium countertransport; apolipoprotein E; hyperlipidemia; polymorphism; Human; Hypertension; Pathogenesis; Red blood cell; Ion transport; Cardiovascular disease; Metabolic diseases; Lipids; Lithium; Hyperlipoproteinemia; Enzymopathy; Genetic determinism; Countercurrent; Sodium; Apolipoprotein E; Hypertriglyceridemia; Dyslipemia; Polymorphism
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/S0895-7061(02)02927-8

Alterations in erythrocyte sodium–lithium countertransport (SLC) activity and its maximal velocity (V max) 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. Cardiovascular risk factors and SLC kinetics were measured in 171 subjects and 69 controls. Apolipoprotein E phenotypes were determined by Western blotting. 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, V max, and sodium affinity (K m) 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 (β = −0.061; P = .01) along with HDL:apoA1 ratio (β = −0.170; P < .001), whereas for the kinetic parameter V max, associations were found with triglyceride (β = 0.029; P = .04), HDL:apoA1 ratio (β = −0.186; P = .03) and the presence of an apoE2 allele (β = −0.089; P = .04). 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 V max.