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

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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

Title: Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke
Author: Seppala, Ilkka; Kleber, Marcus E.; Bevan, Steve; Lyytikainen, Leo-Pekka; Oksala, Niku; Hernesniemi, Jussi A.; Makela, Kari-Matti; Rothwell, Peter M.; Sudlow, Cathie; Dichgans, Martin; Mononen, Nina; Vlachopoulou, Efthymia; Sinisalo, Juha; Delgado, Graciela E.; Laaksonen, Reijo; Koskinen, Tuomas; Scharnagl, Hubert; Kahonen, Mika; Markus, Hugh S.; Maez, Winfried; Lehtimaki, Terho
Contributor: University of Helsinki, Transplantation Laboratory
University of Helsinki, Clinicum
Date: 2016-03-17
Number of pages: 10
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/161139
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.
Subject: GENOME-WIDE ASSOCIATION
ASYMMETRIC DIMETHYLARGININE
NITRIC-OXIDE
SYMMETRIC DIMETHYLARGININE
OXIDATIVE STRESS
BLOOD-PRESSURE
METAANALYSIS
ADMA
POPULATION
MORTALITY
3121 Internal medicine
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