Functional epistatic interaction between rs6046G>A in F7 and rs5355C>T in SELE modifies systolic blood pressure levels.

<h4>Background</h4>Although numerous genetic studies have been performed, only 0.9% of blood pressure phenotypic variance has been elucidated. This phenomenon could be partially due to epistatic interactions. Our aim was to identify epistatic interaction(s) associated with blood pressure...

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Autores principales:	Said El Shamieh, Ndeye Coumba Ndiaye, Maria G Stathopoulou, Helena A Murray, Christine Masson, John V Lamont, Peter Fitzgerald, Athanase Benetos, Sophie Visvikis-Siest
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/acf30578d5f346a48e3129d524a76ee8
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spelling	oai:doaj.org-article:acf30578d5f346a48e3129d524a76ee82021-11-18T07:12:02ZFunctional epistatic interaction between rs6046G>A in F7 and rs5355C>T in SELE modifies systolic blood pressure levels.1932-620310.1371/journal.pone.0040777https://doaj.org/article/acf30578d5f346a48e3129d524a76ee82012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22815813/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Although numerous genetic studies have been performed, only 0.9% of blood pressure phenotypic variance has been elucidated. This phenomenon could be partially due to epistatic interactions. Our aim was to identify epistatic interaction(s) associated with blood pressure levels in a pre-planned two-phase approach.<h4>Methods and results</h4>In a discovery cohort composed of 3,600 French individuals, we found rs6046A allele in F7 associated with decreased blood pressure levels (P≤3.7×10(-3)) and rs5355T allele in SELE associated with decreased diastolic blood pressure levels (P = 5×10(-3)). Both variants interacted in order to influence blood pressure levels (P≤0.048). This interaction was replicated with systolic blood pressure in 4,620 additional European individuals (P = 0.03). Similarly, in this replication cohort, rs6046A was associated with decreased blood pressure levels (P≤8.5×10(-4)). Furthermore, in peripheral blood mononuclear cells of a subsample of 90 supposed healthy individuals, we found rs6046A positively associated with NAMPT mRNA levels (P≤9.1×10(-5)), suggesting an eventual involvement of NAMPT expression in blood pressure regulation. Confirming this hypothesis, further transcriptomic analyses showed that increased NAMPT mRNA levels were positively correlated with ICAM1, SELL, FPR1, DEFA1-3, and LL-37 genes expression (P≤5×10(-3)). The last two mRNA levels were positively associated with systolic blood pressure levels (P≤0.01) and explained 4% of its phenotypic variation.<h4>Conclusion</h4>These findings reveal the importance of epistatic interactions in blood pressure genetics and give new insights for the role of inflammation in its complex regulation.Said El ShamiehNdeye Coumba NdiayeMaria G StathopoulouHelena A MurrayChristine MassonJohn V LamontPeter FitzgeraldAthanase BenetosSophie Visvikis-SiestPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e40777 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Said El Shamieh Ndeye Coumba Ndiaye Maria G Stathopoulou Helena A Murray Christine Masson John V Lamont Peter Fitzgerald Athanase Benetos Sophie Visvikis-Siest Functional epistatic interaction between rs6046G>A in F7 and rs5355C>T in SELE modifies systolic blood pressure levels.
description	<h4>Background</h4>Although numerous genetic studies have been performed, only 0.9% of blood pressure phenotypic variance has been elucidated. This phenomenon could be partially due to epistatic interactions. Our aim was to identify epistatic interaction(s) associated with blood pressure levels in a pre-planned two-phase approach.<h4>Methods and results</h4>In a discovery cohort composed of 3,600 French individuals, we found rs6046A allele in F7 associated with decreased blood pressure levels (P≤3.7×10(-3)) and rs5355T allele in SELE associated with decreased diastolic blood pressure levels (P = 5×10(-3)). Both variants interacted in order to influence blood pressure levels (P≤0.048). This interaction was replicated with systolic blood pressure in 4,620 additional European individuals (P = 0.03). Similarly, in this replication cohort, rs6046A was associated with decreased blood pressure levels (P≤8.5×10(-4)). Furthermore, in peripheral blood mononuclear cells of a subsample of 90 supposed healthy individuals, we found rs6046A positively associated with NAMPT mRNA levels (P≤9.1×10(-5)), suggesting an eventual involvement of NAMPT expression in blood pressure regulation. Confirming this hypothesis, further transcriptomic analyses showed that increased NAMPT mRNA levels were positively correlated with ICAM1, SELL, FPR1, DEFA1-3, and LL-37 genes expression (P≤5×10(-3)). The last two mRNA levels were positively associated with systolic blood pressure levels (P≤0.01) and explained 4% of its phenotypic variation.<h4>Conclusion</h4>These findings reveal the importance of epistatic interactions in blood pressure genetics and give new insights for the role of inflammation in its complex regulation.
format	article
author	Said El Shamieh Ndeye Coumba Ndiaye Maria G Stathopoulou Helena A Murray Christine Masson John V Lamont Peter Fitzgerald Athanase Benetos Sophie Visvikis-Siest
author_facet	Said El Shamieh Ndeye Coumba Ndiaye Maria G Stathopoulou Helena A Murray Christine Masson John V Lamont Peter Fitzgerald Athanase Benetos Sophie Visvikis-Siest
author_sort	Said El Shamieh
title	Functional epistatic interaction between rs6046G>A in F7 and rs5355C>T in SELE modifies systolic blood pressure levels.
title_short	Functional epistatic interaction between rs6046G>A in F7 and rs5355C>T in SELE modifies systolic blood pressure levels.
title_full	Functional epistatic interaction between rs6046G>A in F7 and rs5355C>T in SELE modifies systolic blood pressure levels.
title_fullStr	Functional epistatic interaction between rs6046G>A in F7 and rs5355C>T in SELE modifies systolic blood pressure levels.
title_full_unstemmed	Functional epistatic interaction between rs6046G>A in F7 and rs5355C>T in SELE modifies systolic blood pressure levels.
title_sort	functional epistatic interaction between rs6046g>a in f7 and rs5355c>t in sele modifies systolic blood pressure levels.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/acf30578d5f346a48e3129d524a76ee8
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Functional epistatic interaction between rs6046G>A in F7 and rs5355C>T in SELE modifies systolic blood pressure levels.

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