Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Seppälä, I; Kleber, ME; Bevan, S; Lyytikäinen, LP; Oksala, N; Hernesniemi, JA; Mäkelä, KM; Rothwell, PM; Sudlow, C; Dichgans, M; Mononen, N; Vlachopoulou, E; Sinisalo, J; Delgado, GE; Laaksonen, R; Koskinen, T; Scharnagl, H; Kähönen, M; Markus, HS; März, W; Lehtimäki, T.
Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke.
Sci Rep. 2016; 6(5):23207-23207
Doi: 10.1038/srep23207
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- Co-Autor*innen der Med Uni Graz
- März Winfried
- Scharnagl Hubert
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Alleles -
- Angiography -
- Atrial Fibrillation - genetics
- Atrial Fibrillation - pathology
- Case-Control Studies -
- Chronic Disease -
- Cohort Studies -
- Coronary Vessels - diagnostic imaging
- Female -
- Genotype -
- Humans -
- Logistic Models -
- Male -
- Middle Aged -
- Mutation, Missense -
- Odds Ratio -
- Polymorphism, Single Nucleotide -
- Stroke - genetics
- Stroke - pathology
- Transaminases - genetics
- Transaminases - metabolism