Abstract
Background Epoxide hydrolase 2 (EPHX2) gene coding for soluble epoxide hydrolase is a potential candidate in the pathogenesis of hypertension. Objectives We aimed to assess the association of a missense mutation, R287Q, in EPHX2) gene coding for soluble epoxide hydrolase is a potential candidate in the pathogenesis of hypertension. Methods This study involved 782 patients with primary hypertension and 458 healthy controls. Genotyping was done using TaqMan technique. Activity of soluble epoxide hydrolase fusion proteins was evaluated by the conversion of 11,12-EET to corresponding 11,12-DHET using ELISA kit. Results After taking carriers of R287Q variant GG genotype as a reference, those with GA genotype had a significantly reduced risk of hypertension (adjusted odds ratio: 0.72, 95% confidence interval: 0.56 to 0.93, P = 0.013). Five significant risk factors were identified, including age, body mass index, total cholesterol, homocysteine, and R287Q variant. These five risk factors for hypertension were represented in a nomogram, with a descent prediction accuracy (C-index: 0.833, P = 0.013). Five significant risk factors were identified, including age, body mass index, total cholesterol, homocysteine, and R287Q variant. These five risk factors for hypertension were represented in a nomogram, with a descent prediction accuracy (C-index: 0.833, Conclusions We provide evidence that R287Q mutation in EPHX2 gene was associated with reduced risk of primary hypertension and low activity of soluble epoxide hydrolase.EPHX2) gene coding for soluble epoxide hydrolase is a potential candidate in the pathogenesis of hypertension.
Highlights
Hypertension is a polygenic multifactorial disease [1, 2]
Distributions of age, Body mass index (BMI), systolic blood pressure (SBP), and HCY were significantly higher in cases than in controls (P < 0.05)
Our key findings indicate that the mutation of R287Q variant was associated with low enzyme activity of soluble epoxide hydrolase and reduced risk of having primary hypertension especially under the dominant model of inheritance, indicating that R287Q variant is a functional locus involved in the regulation of EPHX2 gene expression
Summary
Hypertension is a polygenic multifactorial disease [1, 2]. Latest statistics indicate that global prevalence of hypertension has exceeded as high as 1.3 billion [3]. We aimed to assess the association of a missense mutation at exon 8, R287Q (rs751141), in EPHX2 gene with the risk of primary hypertension in Han Chinese and examine the association of this variant with enzyme activity of soluble epoxide hydrolase.
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