The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian population
Numerous studies demonstrated an importance of cytochrome P-450 epoxygenase pathway of arachidonic acids metabolism for the pathogenesis of essential hypertension (EH). The present study was designed to investigate whether common single-nucleotide polymorphisms (SNP) of CYP2C gene subfamily such as...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-05-01
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| Series: | Clinical and Experimental Hypertension |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/10641963.2016.1246562 |
| _version_ | 1797681516360237056 |
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| author | Alexey Polonikov Marina Bykanova Irina Ponomarenko Svetlana Sirotina Anna Bocharova Kseniya Vagaytseva Vadim Stepanov Mikhail Churnosov Olga Bushueva Maria Solodilova Yaroslav Shvetsov Vladimir Ivanov |
| author_facet | Alexey Polonikov Marina Bykanova Irina Ponomarenko Svetlana Sirotina Anna Bocharova Kseniya Vagaytseva Vadim Stepanov Mikhail Churnosov Olga Bushueva Maria Solodilova Yaroslav Shvetsov Vladimir Ivanov |
| author_sort | Alexey Polonikov |
| collection | DOAJ |
| description | Numerous studies demonstrated an importance of cytochrome P-450 epoxygenase pathway of arachidonic acids metabolism for the pathogenesis of essential hypertension (EH). The present study was designed to investigate whether common single-nucleotide polymorphisms (SNP) of CYP2C gene subfamily such as CYP2C8 (rs7909236 and rs1934953), CYP2C9 (rs9332242), and CYP2C19 (rs4244285) are associated with susceptibility to EH in Russian population. A total of 816 unrelated Russian individuals comprising 425 EH patients and 391 normotensive controls were included into the study. Genotyping of SNPs was performed using the MassARRAY 4 system. SNP rs7909236 of CYP2C8 was significantly associated with increased risk of EH (OR adjusted for sex and age was 2.99 95% CI 1.39-6.44, P = 0.005). SNPs rs1934953 CYP2C8 and rs4244285 of CYP2C19 showed association with EH risk but at a borderline statistical significance (P ≤ 0.04). Combination of genotypes CYP2C8 rs7909236 TT and CYP2C19 rs4244285 GG was associated with increased EH risk (OR 3.34 95%CI 1.48-7.51, P = 0.004). Genotype–phenotype correlation analysis showed that the levels of CYP2C8 mRNA were significantly correlated with SNP rs7909236 (P = 0.01). in silico functional prediction analysis revealed the functionality of majority of investigated SNPs. Thus, genes of CYP2C subfamily are important genetic determinants of susceptibility to essential hypertension in Russians. |
| first_indexed | 2024-03-11T23:45:58Z |
| format | Article |
| id | doaj.art-632cf41ebd2747088c62ca561d7fd61f |
| institution | Directory Open Access Journal |
| issn | 1064-1963 1525-6006 |
| language | English |
| last_indexed | 2024-03-11T23:45:58Z |
| publishDate | 2017-05-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Clinical and Experimental Hypertension |
| spelling | doaj.art-632cf41ebd2747088c62ca561d7fd61f2023-09-19T09:24:45ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062017-05-0139430631110.1080/10641963.2016.12465621246562The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian populationAlexey Polonikov0Marina Bykanova1Irina Ponomarenko2Svetlana Sirotina3Anna Bocharova4Kseniya Vagaytseva5Vadim Stepanov6Mikhail Churnosov7Olga Bushueva8Maria Solodilova9Yaroslav Shvetsov10Vladimir Ivanov11Kursk State Medical UniversityKursk State Medical UniversityKursk State Medical UniversityKursk State Medical UniversityResearch Institute for Medical GeneticsResearch Institute for Medical GeneticsResearch Institute for Medical GeneticsBelgorod State UniversityKursk State Medical UniversityKursk State Medical UniversityKursk State Medical UniversityKursk State Medical UniversityNumerous studies demonstrated an importance of cytochrome P-450 epoxygenase pathway of arachidonic acids metabolism for the pathogenesis of essential hypertension (EH). The present study was designed to investigate whether common single-nucleotide polymorphisms (SNP) of CYP2C gene subfamily such as CYP2C8 (rs7909236 and rs1934953), CYP2C9 (rs9332242), and CYP2C19 (rs4244285) are associated with susceptibility to EH in Russian population. A total of 816 unrelated Russian individuals comprising 425 EH patients and 391 normotensive controls were included into the study. Genotyping of SNPs was performed using the MassARRAY 4 system. SNP rs7909236 of CYP2C8 was significantly associated with increased risk of EH (OR adjusted for sex and age was 2.99 95% CI 1.39-6.44, P = 0.005). SNPs rs1934953 CYP2C8 and rs4244285 of CYP2C19 showed association with EH risk but at a borderline statistical significance (P ≤ 0.04). Combination of genotypes CYP2C8 rs7909236 TT and CYP2C19 rs4244285 GG was associated with increased EH risk (OR 3.34 95%CI 1.48-7.51, P = 0.004). Genotype–phenotype correlation analysis showed that the levels of CYP2C8 mRNA were significantly correlated with SNP rs7909236 (P = 0.01). in silico functional prediction analysis revealed the functionality of majority of investigated SNPs. Thus, genes of CYP2C subfamily are important genetic determinants of susceptibility to essential hypertension in Russians.http://dx.doi.org/10.1080/10641963.2016.1246562arachidonic acid metabolismcyp2c8essential hypertensionepoxyeicosatrienoic acidsgenetic susceptibilitysingle-nucleotide polymorphism |
| spellingShingle | Alexey Polonikov Marina Bykanova Irina Ponomarenko Svetlana Sirotina Anna Bocharova Kseniya Vagaytseva Vadim Stepanov Mikhail Churnosov Olga Bushueva Maria Solodilova Yaroslav Shvetsov Vladimir Ivanov The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian population Clinical and Experimental Hypertension arachidonic acid metabolism cyp2c8 essential hypertension epoxyeicosatrienoic acids genetic susceptibility single-nucleotide polymorphism |
| title | The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian population |
| title_full | The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian population |
| title_fullStr | The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian population |
| title_full_unstemmed | The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian population |
| title_short | The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian population |
| title_sort | contribution of cyp2c gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in russian population |
| topic | arachidonic acid metabolism cyp2c8 essential hypertension epoxyeicosatrienoic acids genetic susceptibility single-nucleotide polymorphism |
| url | http://dx.doi.org/10.1080/10641963.2016.1246562 |
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