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Edgar Allan Poe/Sullivan's Island Library
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West Ashley Library
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Wando Mount Pleasant Library
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Village Library
9 a.m. - 1 p.m.
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St. Paul's/Hollywood Library
9 a.m. - 8 p.m.
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Otranto Road Library
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Hurd/St. Andrews Library
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Two polymorphisms in the Cx40 promoter are associated with hypertension and left ventricular hypertrophy preferentially in men.
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- Author(s): Schmidt, Kjestine (AUTHOR); Kaiser, Frank J (AUTHOR); Erdmann, Jeanette (AUTHOR); Wit, Cor de (AUTHOR)
- Source:
Clinical & Experimental Hypertension. Nov2015, Vol. 37 Issue 7, p580-586. 7p. - Source:
- Additional Information
- Subject Terms:
- Abstract: Background: Lack of connexin40, a gap junction protein expressed in endothelial and renin-producing cells, results in hypertension and cardiac hypertrophy in mice due to unleashed renin production caused by disruption of the pressure-induced feedback inhibition. We analysed humanGJA5consisting of two exons (exon1A or 1B and exon2) in a selected cohort identified by a single nucleotide polymorphism (SNP) in theGJA5intron for polymorphisms and putative association with hypertension and left ventricular hypertrophy (LVH).Methods: Individuals carrying a SNP in the intron ofGJA5(rs791295) were selected from the MONICA/KORA cohort (n = 1677) and searched forGJA5polymorphisms. We accessed DNA of 178 probands, of which 26 suffered from LVH, 112 were hypertensive and 29 normotensive (unknown: 11).Results: Sequencing of theGJA5coding region did not reveal alterations suggesting the expression of functional connexin40 in all probands. Sequencing of the upstream region of transcript 1A including exon1A revealed two previously described linked SNPs (rs35594137 −44G>A; rs11552588 + 71A>G) at an increased frequency. Moreover, the rare genotype was significantly associated with hypertension and LVH with a preponderance in men. Functional analysis in a reporter gene assay verified promoter activity, however, it was unchanged by the identified SNPs after expressing respective reporter constructs in HeLa and human endothelial cells.Conclusion: We suggest to consider the −44G>A SNP upstream of the connexin40 transcript 1A indeed as a risk factor for hypertension in men. However, the underlying mechanisms remain unclear but animal data suggest that renin-producing cells may be involved and contribute to hypertension. [ABSTRACT FROM AUTHOR]
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