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

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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.

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Acknowledgments

The authors would like to thank all the patients who participated in this study. This work was supported by DUNK01/2/28.12.2009 “National University Complex in Biomedical and Translational Research,” funded by National Science Fund, Ministry of Education and Science and Grant № D-1/2011–MU Pleven, Bulgaria.

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Authors and Affiliations

  1. Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave str, 1431, Sofia, Bulgaria

    Reni Tzveova, Ivan Popov, Olga Beltheva, Vanio Mitev & Radka Kaneva

  2. Second Department of Cardiology, UMBAL “Dr. G. Stranski”, Pleven, Pleven, Bulgaria

    Galya Naydenova

  3. Department of Internal Medicine, Clinic of Cardiology, Medical University, Sofia, Sofia, Bulgaria

    Teodora Yaneva, Georgi Dimitrov & Rumiana Tarnovska-Kadreva

  4. Clinical Center of Endocrinology and Gerontology, Medical University, Sofia, Sofia, Bulgaria

    Silviya Vandeva & Yoanna Matrozova

  5. Department of Experimental and Clinical Pharmacology, Dermatology and Venereology, Medical University, Pleven, Pleven, Bulgaria

    Diana Pendicheva-Duhlenska

  6. Department of Medical Chemistry and Biochemistry, Medical University, Sofia, Sofia, Bulgaria

    Cyrill Naydenov

  7. Department of Cardiovascular Surgery, University Hospital of Cardiovascular Surgery and Cardiology “St. Ekaterina”, Sofia, Sofia, Bulgaria

    Gencho Nachev

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  1. Reni Tzveova
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  2. Galya Naydenova
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  3. Teodora Yaneva
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  4. Georgi Dimitrov
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  7. Diana Pendicheva-Duhlenska
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  8. Ivan Popov
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  12. Gencho Nachev
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  13. Vanio Mitev
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  14. Radka Kaneva
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Correspondence to Reni Tzveova.

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The authors declare that the current research has been approved by the Ethics Committees of Medical University of Sofia and Medical University of Pleven and has been performed in compliance with the ethical standards laid down in the Declaration of Helsinki and the national ethical standards and regulations.

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Tzveova, R., Naydenova, G., Yaneva, T. et al. Gender-Specific Effect of CYP2C8*3 on the Risk of Essential Hypertension in Bulgarian Patients. Biochem Genet 53, 319–333 (2015). https://doi.org/10.1007/s10528-015-9696-7

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  • DOI: https://doi.org/10.1007/s10528-015-9696-7

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