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; Lehtimäki, Terho (2016): Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke. In: Scientific Reports, Vol. 6, 23207 |
| 800kB |
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.
Item Type: | Journal article |
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Faculties: | Medicine > Institute for Stroke and Dementia Research (ISD) |
Subjects: | 600 Technology > 610 Medicine and health |
URN: | urn:nbn:de:bvb:19-epub-37992-9 |
ISSN: | 2045-2322 |
Language: | English |
ID Code: | 37992 |
Deposited On: | 04. May 2017 13:11 |
Last Modified: | 04. Nov 2020 14:45 |
- BASE
- 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
- Lehtimäki, Terho
- Google Scholar
- 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
- Lehtimäki, Terho