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

Seppälä, Ilkka, Kleber, Marcus E., Bevan, Steve , Lyytikäinen, Leo-Pekka, Oksala, Niku, Hernesniemi, Jussi A., Mäkelä, Kari-Matti, Rothwell, Peter M., Sudlow, Cathie, Dichgans, Martin, Mononen, Nina, Vlachopoulou, Efthymia, Sinisalo, Juha, Delgado, Graciela E., Laaksonen, Reijo, Koskinen, Tuomas, Scharnagl, Hubert, Kähönen, Mika, Markus, Hugh S., März, Winfried and Lehtimäki, Terho (2016) Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke. Scientific Reports, 6 . p. 23207. ISSN 2045-2322

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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.

Keywords:Stroke, NotOAChecked
Subjects:C Biological Sciences > C400 Genetics
Divisions:College of Science > School of Life Sciences
ID Code:23602
Deposited On:29 Jul 2016 14:25

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