Gender-Specific Effect of CYP2C8*3 on the Risk of Essential Hypertension in Bulgarian Patients

We conducted a case-control study to determine the contribution of polymorphisms in CYP2C8 (CYP2C8*3) and CYP2J2 (CYP2J2*7) to increased risk of coronary artery disease and essential hypertension in Bulgarians. The current analysis included 192 unrelated hypertensive patients, 261 patients with angiographically documented CAD (153 with myocardial infarction and 108 without myocardial infarction), and 496 population controls. The CYP2C8*3 and CYP2J2*7 polymorphisms were genotyped by TaqMan SNP Genotyping Assay. PLINK version 1.07 was used for the statistical analysis. No overall association was observed for the studied polymorphisms with coronary artery disease and essential hypertension. The frequency of -50T mutant allele of CYP2J2*7 was significantly higher in male with coronary artery disease without history of myocardial infarction (OR 2.16 95% CI 1.04-4.48 p = 0.035) compared to population control group, but this association did not survive after Bonferroni correction (p (adj) = 0.07). A significant association of CYP2C8*3 allele with increased risk of essential hypertension has found in men (OR 2.12 95% CI 1.18-3.81 p = 0.015) and this relationship remained significant after adjustment for multiple comparisons (p (adj) = 0.03). This is the first study showing significant gene-sex interaction for CYP2C8*3 with twofold increase in the relative risk of essential hypertension and a similar tendency for CYP2J2*7 associated with coronary artery disease without myocardial infarction in Bulgarian males. The association is not seen in females and in the whole group of patients. This result could be partly explained by the effect of estrogens on the vascular tone of coronary arteries and CYP2C8 gene expression.