Polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia
Abstract This study aimed to determine possible association of eight polymorphisms of seven MMP genes with essential hypertension (EH) in a Caucasian population of Central Russia. Eight SNPs of the MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, and MMP12 genes and their gene–gene (epistatic) interactions were...
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2021
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oai:doaj.org-article:cdaefe5f8d7b473899110a60a908962e2021-12-02T13:20:02ZPolymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia10.1038/s41598-021-84645-42045-2322https://doaj.org/article/cdaefe5f8d7b473899110a60a908962e2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84645-4https://doaj.org/toc/2045-2322Abstract This study aimed to determine possible association of eight polymorphisms of seven MMP genes with essential hypertension (EH) in a Caucasian population of Central Russia. Eight SNPs of the MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, and MMP12 genes and their gene–gene (epistatic) interactions were analyzed for association with EH in a cohort of 939 patients and 466 controls using logistic regression and assuming additive, recessive, and dominant genetic models. The functional significance of the polymorphisms associated with EH and 114 variants linked to them (r2 ≥ 0.8) was analyzed in silico. Allele G of rs11568818 MMP7 was associated with EH according to all three genetic models (OR = 0.58–0.70, pperm = 0.01–0.03). The above eight SNPs were associated with the disorder within 12 most significant epistatic models (OR = 1.49–1.93, pperm < 0.02). Loci rs1320632 MMP8 and rs11568818 MMP7 contributed to the largest number of the models (12 and 10, respectively). The EH-associated loci and 114 SNPs linked to them had non-synonymous, regulatory, and eQTL significance for 15 genes, which contributed to the pathways related to metalloendopeptidase activity, collagen degradation, and extracellular matrix disassembly. In summary, eight studied SNPs of MMPs genes were associated with EH in the Caucasian population of Central Russia.Maria MoskalenkoIrina PonomarenkoEvgeny ReshetnikovVolodymyr DvornykMikhail ChurnosovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q Maria Moskalenko Irina Ponomarenko Evgeny Reshetnikov Volodymyr Dvornyk Mikhail Churnosov Polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia |
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Abstract This study aimed to determine possible association of eight polymorphisms of seven MMP genes with essential hypertension (EH) in a Caucasian population of Central Russia. Eight SNPs of the MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, and MMP12 genes and their gene–gene (epistatic) interactions were analyzed for association with EH in a cohort of 939 patients and 466 controls using logistic regression and assuming additive, recessive, and dominant genetic models. The functional significance of the polymorphisms associated with EH and 114 variants linked to them (r2 ≥ 0.8) was analyzed in silico. Allele G of rs11568818 MMP7 was associated with EH according to all three genetic models (OR = 0.58–0.70, pperm = 0.01–0.03). The above eight SNPs were associated with the disorder within 12 most significant epistatic models (OR = 1.49–1.93, pperm < 0.02). Loci rs1320632 MMP8 and rs11568818 MMP7 contributed to the largest number of the models (12 and 10, respectively). The EH-associated loci and 114 SNPs linked to them had non-synonymous, regulatory, and eQTL significance for 15 genes, which contributed to the pathways related to metalloendopeptidase activity, collagen degradation, and extracellular matrix disassembly. In summary, eight studied SNPs of MMPs genes were associated with EH in the Caucasian population of Central Russia. |
format |
article |
author |
Maria Moskalenko Irina Ponomarenko Evgeny Reshetnikov Volodymyr Dvornyk Mikhail Churnosov |
author_facet |
Maria Moskalenko Irina Ponomarenko Evgeny Reshetnikov Volodymyr Dvornyk Mikhail Churnosov |
author_sort |
Maria Moskalenko |
title |
Polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia |
title_short |
Polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia |
title_full |
Polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia |
title_fullStr |
Polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia |
title_full_unstemmed |
Polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia |
title_sort |
polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a caucasian population of central russia |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/cdaefe5f8d7b473899110a60a908962e |
work_keys_str_mv |
AT mariamoskalenko polymorphismsofthematrixmetalloproteinasegenesareassociatedwithessentialhypertensioninacaucasianpopulationofcentralrussia AT irinaponomarenko polymorphismsofthematrixmetalloproteinasegenesareassociatedwithessentialhypertensioninacaucasianpopulationofcentralrussia AT evgenyreshetnikov polymorphismsofthematrixmetalloproteinasegenesareassociatedwithessentialhypertensioninacaucasianpopulationofcentralrussia AT volodymyrdvornyk polymorphismsofthematrixmetalloproteinasegenesareassociatedwithessentialhypertensioninacaucasianpopulationofcentralrussia AT mikhailchurnosov polymorphismsofthematrixmetalloproteinasegenesareassociatedwithessentialhypertensioninacaucasianpopulationofcentralrussia |
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