Abstract

The present study was designed to test whether common polymorphism G-50T within the promoter of human CYP2J2 gene is associated with increased risk of essential hypertension in a Russian population. We studied 576 unrelated subjects, including 295 patients with hypertension and 281 healthy subjects. Genotyping for polymorphism G-50T of the CYP2J2 gene was performed by polymerase chain reaction and restriction fragment length polymorphism techniques. The frequency of a −50T variant allele of CYP2J2 gene was significantly higher in patients with hypertension versus healthy controls (OR 4.03 95%CI 1.80–9.04 p=0.0004). The association of a −50GT genotype with hypertension remained significant after adjustment for age, gender and family history of hypertension by multivariate logistic regression (OR 4.78 95%CI 1.87–12.27 p=0.001). It has been found that OR for −50GT genotype × gender interaction (OR 4.48 95%CI 1.93–10.39 p=0.00048) was slightly higher than OR for −50GT genotype (OR 4.43 95%CI 1.91–10.29 p=0.00052), suggesting a weak effect of gender on the risk of hypertension in the heterozygous carriers of −50GT genotype. A family history of hypertension has no effect on the association between a −50GT genotype and hypertension. In present study we demonstrate for the first time that a CYP2J2*7 allele of the CYP2J2 gene is clearly associated with an increased risk of essential hypertension. Furthermore, this study highlights the importance of P-450 epoxygenase pathway of arachidonic acid metabolism in the pathogenesis of hypertensive disease.

Highlights

  • In recent years, increasing interest has been focused on the vasoactive products of arachidonic acid (AA) derived from cytochrome P450 epoxygenase pathway, and impressive progress has been achieved in the understanding of their role both in vascular homeostasis and development of essential hypertension (EH) [4,14,22, 28,33,36,38]

  • The frequency of a −50T mutant allele of cytochrome P-450 2J2 (CYP2J2) gene was significantly higher in EH patients versus healthy subjects

  • We investigated an association between polymorphism G-50T of the CYP2J2 gene and essential hypertension in an ethnically homogeneous Russian population

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Summary

Introduction

In recent years, increasing interest has been focused on the vasoactive products of arachidonic acid (AA) derived from cytochrome P450 epoxygenase pathway, and impressive progress has been achieved in the understanding of their role both in vascular homeostasis and development of essential hypertension (EH) [4,14,22, 28,33,36,38]. Transport in cardiovascular and renal tissues, suggesting a crucial role of epoxygenase-derived eicosanoids in blood pressure regulation [7,16,32,36]. EETs have been suggested to increase the proliferation of various cell types, including vascular smooth muscle cells and endothelial cells demonstrating a potential role of cytochrome P450 eicosanoids to promote vascular remodeling [13,29]

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