[PP.07.15] A PROMOTER POLYMORPHISM -271C > A OF THE CYP2C8 GENE IS ASSOCIATED WITH INCREASED RISK OF ESSENTIAL HYPERTENSION: A PILOT STUDY

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Abstract

Objective:

The purpose of our pilot study was to investigate associations between polymorphisms of the CYP2C8 gene with susceptibility to essential hypertension (EH) in Russian population.

Design and method:

A genetic association study of common polymorphisms of the CYP2C8 gene with essential hypertension in Russian population. A total of 1 459 unrelated Russian individuals (Kursk region) including 845 EH patients and 614 age and sex matched healthy subjects with normal blood pressure were recruited for this study. Two common polymorphisms −271C > A (rs7909236) and 404G > A (rs1934953) of the CYP2C8 gene were genotyped using the MassARRAY 4 system.

Results:

Genotype frequencies of CYP2C8 gene polymorphisms were in agreement with Hardy–Weinberg equilibrium in all groups. We found that variant genotypes −271CA plus AA were significantly associated with increased hypertension risk (odds ratio = 1.31; 95% confidence interval: 1.04–1.64, P = 0.02). The association remained a statistically significant after adjustment for age, sex and body mass index by a multiple logistic regression analyses (P = 0.03). Moreover, a homozygous variant genotype 404AA tended to be associated with an increased risk of EH (odds ratio = 1.41; 95% confidence interval: 0.98–2.02, P = 0.06). However, no significant association was found between rs1934953 and EH after adjusting for the covariates.

Conclusions:

CYP2C8 is a cytochrome P450 enzyme involving in the generation epoxyeicosatrienic acids (EETs) from arachidonic acid, an important biochemical pathway creating mediators of inflammation and blood pressure regulation. A polymorphism −271C > A located in the promoter region of the CYP2C8 results in the creation of a C/EBPalpha transcription factor consensus sequence influencing a transcriptional activity of the gene. The −271C > A polymorphism of the CYP2C8 gene may contribute to hypertension susceptibility through the mechanisms related with biosynthesis of vascular EETs and those inducing oxidative stress by reactive oxygen species which are generated during the epoxidation of arachidonic acid by the CYP450 epoxygenase. Our pilot study is the first to show that the −271C > A polymorphism of the CYP2C8 gene is associated with increased risk of hypertension. The study was supported by Russian Science Foundation (number 15-15-10010).

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