Journal article
Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 781.4KB, Terms of use)
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- Publisher copy:
- 10.1038/srep23207
Authors
- Journal:
- Scientific reports More from this journal
- Volume:
- 6
- Issue:
- 1
- Pages:
- 23207
- Publication date:
- 2016-03-17
- Acceptance date:
- 2016-03-02
- DOI:
- EISSN:
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2045-2322
- ISSN:
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2045-2322
- Pmid:
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26984639
- Language:
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English
- Keywords:
- Pubs id:
-
pubs:611655
- UUID:
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uuid:bdd19d2b-4d4c-4e8a-8cd2-03fe7baf9ad0
- Local pid:
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pubs:611655
- Source identifiers:
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611655
- Deposit date:
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2016-12-15
Terms of use
- Copyright holder:
- Seppälä et al
- Copyright date:
- 2016
- Notes:
- © The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Licence:
- CC Attribution (CC BY)
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