Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke

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dc.contributor.author Seppala, Ilkka
dc.contributor.author Kleber, Marcus E.
dc.contributor.author Bevan, Steve
dc.contributor.author Lyytikainen, Leo-Pekka
dc.contributor.author Oksala, Niku
dc.contributor.author Hernesniemi, Jussi A.
dc.contributor.author Makela, Kari-Matti
dc.contributor.author Rothwell, Peter M.
dc.contributor.author Sudlow, Cathie
dc.contributor.author Dichgans, Martin
dc.contributor.author Mononen, Nina
dc.contributor.author Vlachopoulou, Efthymia
dc.contributor.author Sinisalo, Juha
dc.contributor.author Delgado, Graciela E.
dc.contributor.author Laaksonen, Reijo
dc.contributor.author Koskinen, Tuomas
dc.contributor.author Scharnagl, Hubert
dc.contributor.author Kahonen, Mika
dc.contributor.author Markus, Hugh S.
dc.contributor.author Maez, Winfried
dc.contributor.author Lehtimaki, Terho
dc.date.accessioned 2016-04-11T05:58:02Z
dc.date.available 2016-04-11T05:58:02Z
dc.date.issued 2016-03-17
dc.identifier.citation Seppala , I , Kleber , M E , Bevan , S , Lyytikainen , L-P , Oksala , N , Hernesniemi , J A , Makela , K-M , Rothwell , P M , Sudlow , C , Dichgans , M , Mononen , N , Vlachopoulou , E , Sinisalo , J , Delgado , G E , Laaksonen , R , Koskinen , T , Scharnagl , H , Kahonen , M , Markus , H S , Maez , W & Lehtimaki , T 2016 , ' Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke ' , Scientific Reports , vol. 6 , 23207 . https://doi.org/10.1038/srep23207
dc.identifier.other PURE: 61945208
dc.identifier.other PURE UUID: 3273f8f3-53fd-40a7-a528-7293658ebc8c
dc.identifier.other WOS: 000372146400003
dc.identifier.other Scopus: 84962624737
dc.identifier.other ORCID: /0000-0002-0169-5137/work/29512886
dc.identifier.uri http://hdl.handle.net/10138/161139
dc.description.abstract Asymmetric and symmetric dimethylarginines (ADMA and SDMA) impair nitric oxide bioavailability and have been implicated in the pathogenesis of atrial fibrillation (AF). Alanine-glyoxylate aminotransferase 2 (AGXT2) is the only enzyme capable of metabolizing both of the dimethylarginines. We hypothesized that two functional AGXT2 missense variants (rs37369, V140I; rs16899974, V498L) are associated with AF and its cardioembolic complications. Association analyses were conducted using 1,834 individulas with AF and 7,159 unaffected individuals from two coronary angiography cohorts and a cohort comprising patients undergoing clinical exercise testing. In coronary angiography patients without structural heart disease, the minor A allele of rs16899974 was associated with any AF (OR = 2.07, 95% CI 1.59-2.68), and with paroxysmal AF (OR = 1.98, 95% CI 1.44-2.74) and chronic AF (OR = 2.03, 95% CI 1.35-3.06) separately. We could not replicate the association with AF in the other two cohorts. However, the A allele of rs16899974 was nominally associated with ischemic stroke risk in the meta-analysis of WTCCC2 ischemic stroke cohorts (3,548 cases, 5,972 controls) and with earlier onset of first-ever ischemic stroke (360 cases) in the cohort of clinical exercise test patients. In conclusion, AGXT2 variations may be involved in the pathogenesis of AF and its age-related thromboembolic complications. en
dc.format.extent 10
dc.language.iso eng
dc.relation.ispartof Scientific Reports
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject GENOME-WIDE ASSOCIATION
dc.subject ASYMMETRIC DIMETHYLARGININE
dc.subject NITRIC-OXIDE
dc.subject SYMMETRIC DIMETHYLARGININE
dc.subject OXIDATIVE STRESS
dc.subject BLOOD-PRESSURE
dc.subject METAANALYSIS
dc.subject ADMA
dc.subject POPULATION
dc.subject MORTALITY
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke en
dc.type Article
dc.contributor.organization Transplantation Laboratory
dc.contributor.organization Medicum
dc.contributor.organization Clinicum
dc.contributor.organization University of Helsinki
dc.contributor.organization Department of Medicine
dc.contributor.organization Kardiologian yksikkö
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/srep23207
dc.relation.issn 2045-2322
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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