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Association between arterial stiffness and variations in estrogen-related genes

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dc.contributor.author Peter, Inga
dc.contributor.author Kelley-Hedgepeth, Alyson
dc.contributor.author Huggins, Gordon S.
dc.contributor.author Housman, David E.
dc.contributor.author Mendelsohn, Michael E.
dc.contributor.author Vita, Joseph A.
dc.contributor.author Vasan, Ramachandran S.
dc.contributor.author Levy, Daniel
dc.contributor.author Benjamin, Emelia J.
dc.contributor.author Mitchell, Gary F.
dc.date.accessioned 2012-10-05T18:57:12Z
dc.date.available 2012-10-05T18:57:12Z
dc.date.issued 2009-10
dc.identifier.issn 0950-9240
dc.identifier.issn 0950-9240
dc.identifier.uri http://hdl.handle.net/1721.1/73662
dc.description available in PMC 2010 April 1. en_US
dc.description.abstract Increased arterial stiffness and wave reflection have been identified as cardiovascular disease risk factors. In light of significant sex differences and the moderate heritability of vascular function measures, we hypothesized that variation in the genes coding for oestrogen receptors α (ESR1) and β (ESR2) and aromatase (CYP19A1) is associated with aortic stiffness and pressure wave reflection as measured by non-invasive arterial tonometry. In all, 1261 unrelated Framingham Offspring Study participants who attended the seventh examination cycle (mean age 62±10 years, 52% women) and had arterial tonometry and genotyping data were included in the study. Analysis of covariance was used to assess the association of polymorphisms with forward wave amplitude, augmented pressure, augmentation index (AI), carotid–femoral pulse wave velocity and mean arterial pressure with adjustment for potential confounders. In the sex-pooled analysis, those homozygous for the minor allele at any of four ESR1 variants that were in strong linkage disequilibrium ((TA)n, rs2077647, rs2234693 and rs9340799) had on an average 18% higher augmented pressure and 16% greater AI compared with carriers of one or two major alleles (P=0.0002–0.01). A similar magnitude of association was detected in those homozygous for the common allele at two ESR2 single-nucleotide polymorphisms (P=0.007–0.02). Our results are consistent with the hypothesis that variation in ESR1 and ESR2, but not CYP19A1, is associated with an increased wave reflection that may contribute to associations between these variants and adverse clinical events demonstrated earlier. Our findings will need to be replicated in additional cohorts. en_US
dc.language.iso en_US
dc.publisher Nature Publishing Group en_US
dc.relation.isversionof http://dx.doi.org/10.1038/jhh.2009.1 en_US
dc.rights Creative Commons Attribution-Noncommercial-Share Alike 3.0 en_US
dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/ en_US
dc.source PMC en_US
dc.title Association between arterial stiffness and variations in estrogen-related genes en_US
dc.type Article en_US
dc.identifier.citation Peter, I et al. “Association Between Arterial Stiffness and Variations in Oestrogen-related Genes.” Journal of Human Hypertension 23.10 (2009): 636–644. Web. en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Biology en_US
dc.contributor.department David H. Koch Institute for Integrative Cancer Research at MIT en_US
dc.contributor.mitauthor Housman, David E.
dc.relation.journal Journal of Human Hypertension en_US
dc.identifier.mitlicense OPEN_ACCESS_POLICY en_US
dc.eprint.version Author's final manuscript en_US
dc.type.uri http://purl.org/eprint/type/JournalArticle en_US
eprint.status http://purl.org/eprint/status/PeerReviewed en_US
dspace.orderedauthors Peter, I; Kelley-Hedgepeth, A; Huggins, G S; Housman, D E; Mendelsohn, M E; Vita, J A; Vasan, R S; Levy, D; Benjamin, E J; Mitchell, G F en


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