title: Gender-Specific Effect of CYP2C8*3 on the Risk of Essential Hypertension in Bulgarian Patients.
abstract: 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.
authors.affiliation: Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave str, 1431, Sofia, Bulgaria. renitzveova@abv.bg.
authors.forename: Reni
authors.initials: R
authors.lastname: Tzveova
authors.affiliation: Second Department of Cardiology, UMBAL "Dr. G. Stranski", Pleven, Pleven, Bulgaria.
authors.forename: Galya
authors.initials: G
authors.lastname: Naydenova
authors.affiliation: Department of Internal Medicine, Clinic of Cardiology, Medical University, Sofia, Sofia, Bulgaria.
authors.forename: Teodora
authors.initials: T
authors.lastname: Yaneva
authors.affiliation: Department of Internal Medicine, Clinic of Cardiology, Medical University, Sofia, Sofia, Bulgaria.
authors.forename: Georgi
authors.initials: G
authors.lastname: Dimitrov
authors.affiliation: Clinical Center of Endocrinology and Gerontology, Medical University, Sofia, Sofia, Bulgaria.
authors.forename: Silviya
authors.initials: S
authors.lastname: Vandeva
authors.affiliation: Clinical Center of Endocrinology and Gerontology, Medical University, Sofia, Sofia, Bulgaria.
authors.forename: Yoanna
authors.initials: Y
authors.lastname: Matrozova
authors.affiliation: Department of Experimental and Clinical Pharmacology, Dermatology and Venereology, Medical University, Pleven, Pleven, Bulgaria.
authors.forename: Diana
authors.initials: D
authors.lastname: Pendicheva-Duhlenska
authors.affiliation: Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave str, 1431, Sofia, Bulgaria.
authors.forename: Ivan
authors.initials: I
authors.lastname: Popov
authors.affiliation: Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave str, 1431, Sofia, Bulgaria.
authors.forename: Olga
authors.initials: O
authors.lastname: Beltheva
authors.affiliation: Department of Medical Chemistry and Biochemistry, Medical University, Sofia, Sofia, Bulgaria.
authors.forename: Cyrill
authors.initials: C
authors.lastname: Naydenov
authors.affiliation: Department of Internal Medicine, Clinic of Cardiology, Medical University, Sofia, Sofia, Bulgaria.
authors.forename: Rumiana
authors.initials: R
authors.lastname: Tarnovska-Kadreva
authors.affiliation: Department of Cardiovascular Surgery, University Hospital of Cardiovascular Surgery and Cardiology "St. Ekaterina", Sofia, Sofia, Bulgaria.
authors.forename: Gencho
authors.initials: G
authors.lastname: Nachev
authors.affiliation: Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave str, 1431, Sofia, Bulgaria.
authors.forename: Vanio
authors.initials: V
authors.lastname: Mitev
authors.affiliation: Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave str, 1431, Sofia, Bulgaria.
authors.forename: Radka
authors.initials: R
authors.lastname: Kaneva
mesh_terms: D000328:Adult; D002031:Bulgaria; D003324:Coronary Artery Disease / Q000235:genetics; D065727:Cytochrome P-450 CYP2C8 / Q000235:genetics / Q000378:metabolism*; D000075222:Essential Hypertension; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
chemical_list: D065727:Cytochrome P-450 CYP2C8
keywords: CYP2C8; CYP2J2; Coronary artery disease; Essential hypertension