Abstract
BackgroundErythropoietin-producing human hepatocellular (Eph) receptors might contribute to the development of atherosclerosis. A genome-wide association study indicated that the Eph receptor A6 gene (EPHA6) associated with at least 1 blood pressure (BP) phenotype. The objective of the present study was to determine whether EPHA6 is a novel candidate gene for hypertension in a Korean population.MethodsA total 2146 study participants with normotension and hypertension were included. Genotype data were obtained using a Korean Chip. To assess the association between single-nucleotide polymorphisms (SNPs) and BP, we performed a linear regression analysis, which showed that rs4850755 in the EPHA6 gene was the SNP most highly associated with both systolic and diastolic BP.ResultsThe presence of the TT genotype of the EPHA6 rs4857055 C > T SNP was associated with a higher risk of hypertension after adjusting for age, sex, body mass index (BMI), smoking, and drinking [odds ratio 1.533, P = 0.001]. In the control group, significant associations were observed between systolic BP and the rs4857055 polymorphism and between diastolic BP and the rs4857055 polymorphism. In the hypertension group, a significant association was observed between systolic BP and the rs4857055 polymorphism. In the hypertension group, subjects with the TT genotype showed significantly higher systolic BP than CC subjects. Additionally, in the hypertension group, TT carriers showed a higher tendency of serum triglyceride (P = 0.069) and significantly higher apolipoprotein B (P = 0.015) and smaller low-density lipoprotein (LDL) particle size (P < 0.001) than either TC or CC subjects.ConclusionsThese results could suggest that the EPHA6 rs4857055 C > T SNP is a novel candidate gene for hypertension in the Korean population. Additionally, the TT genotype could be associated with hypertriglyceridemia and small LDL particle size in hypertension.
Highlights
Erythropoietin-producing human hepatocellular (Eph) receptors might contribute to the development of atherosclerosis
Because a close relationship exists between Ephs/ ephrins and blood pressure (BP), between Eph receptor A6 gene (EPHA6) and BP [18], specific EPHA6 Single-nucleotide polymorphism (SNP) genotypes in humans could be associated with BP
The presence of the TT genotype of the EPHA6 rs4857055 C > T SNP was associated with a higher risk of hypertension [odds ratio (OR) 1.415, P = 0.003] (Table 2)
Summary
Erythropoietin-producing human hepatocellular (Eph) receptors might contribute to the development of atherosclerosis. A genome-wide association study indicated that the Eph receptor A6 gene (EPHA6) associated with at least 1 blood pressure (BP) phenotype. The Eph/ephrin molecule is important for the developing cardiovascular system, as shown by the presence of heart and blood vessel defects resulting from knockout of Eph receptors or ephrins [10]. Eph receptors/ephrins expressed in blood vessels and their counterparts in immune cells are associated with inflammatory processes ranging from increased endothelial permeability and the mediation of inflammatory cell adhesion and migration to atherosclerotic plaque development [11,12,13,14]. The Korean Chip (K-CHIP) was developed as a low-cost customized chip that is optimized for genetic studies on disease and complex traits in the Korean population. The objective of the present study was to determine whether EPHA6 is a novel candidate gene for hypertension in the Korean population
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