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A comprehensive study revealed SNP–SNP interactions and a sex-dependent relationship between polymorphisms of the CYP2J2 gene and hypertension risk

Hypertension Research volume 42, pages 257–272 (2019)Cite this article

Abstract

This study investigated whether common polymorphisms of cytochrome P450 2J2 (CYP2J2), a major enzyme that controls the biosynthesis of vasoactive epoxyeicosatrienoic acids, are collectively involved in the molecular basis of essential hypertension (EH). A total of 2314 unrelated Russian subjects from the Kursk (discovery sample: 913 EH patients and 645 controls) and Belgorod (replication sample: 345 EH patients and 411 controls) regions were recruited for this study. Eight single nucleotide polymorphisms (SNPs), including rs890293, rs11572182, rs10493270, rs1155002, rs2280275, rs7515289, rs11572325, and rs10889162, of CYP2J2 were genotyped using the MassARRAY 4 system and TaqMan-based assays. Significant associations were identified among the SNPs rs890293 (OR = 2.17, 95%CI 1.30–3.65), rs2280275 (OR = 1.59, 95%CI 1.10–2.37) and rs11572325 (OR = 1.89, 95%CI 1.22–2.95) and the risk of EH in females from the Kursk population. Sixteen CYP2J2 genotype combinations only showed significant associations with EH risk only in females. A common haplotype, T-T-G-C-C-C-T-A, increased the risk of EH in females. The bioinformatic analysis enabled identification of the SNPs that possess regulatory potential and/or are located within the binding sites for multiple transcription factors that play roles in the pathways involved in hypertension pathogenesis. Moreover, the polymorphisms rs890293, rs2280275, and rs11572325 were found to be significantly associated with hypertension risk in the Belgorod population. In conclusion, the rs2280275 and rs11572325 SNPs of CYP2J2 may be considered novel genetic markers of hypertension, at least in Russian women. However, sex-specific associations between CYP2J2 gene polymorphisms and hypertension require further investigation to clarify the specific genetic and/or environmental factors that are responsible for the increased disease susceptibility of women compared to that of men.

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Acknowledgements

The study was supported by the Russian Science Foundation (№15-15-10010).

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Authors and Affiliations

  1. Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx St., Kursk, 305041, Russian Federation

    Alexey V. Polonikov, Irina V. Ponomarenko, Svetlana S. Sirotina & Maria A. Solodilova

  2. Laboratory of Statistical Genetics and Bioinformatics, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 18 Yamskaya St., Kursk, 305041, Russian Federation

    Alexey V. Polonikov

  3. Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 18 Yamskaya St., Kursk, 305041, Russian Federation

    Marina A. Bykanova

  4. Evolutionary Genetics Laboratory, Research Institute of Medical Genetics, Tomsk National Medical Research Center, 10 Nabereznaya Ushaiki, Tomsk, 634050, Russian Federation

    Anna V. Bocharova, Kseniya V. Vagaytseva & Vadim A. Stepanov

  5. Laboratory of Biochemical Genetics and Metabolomics, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 18 Yamskaya St., Kursk, 305041, Russian Federation

    Iuliia E. Azarova

  6. Department of Medical Biological Disciplines, Belgorod State University, 85 Pobeda St., Belgorod, 308015, Russian Federation

    Mikhail I. Churnosov

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Polonikov, A.V., Ponomarenko, I.V., Bykanova, M.A. et al. A comprehensive study revealed SNP–SNP interactions and a sex-dependent relationship between polymorphisms of the CYP2J2 gene and hypertension risk. Hypertens Res 42, 257–272 (2019). https://doi.org/10.1038/s41440-018-0142-1

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