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Associations of functional alanine-glyoxylate aminotransferase 2 gene variants
with atrial fibrillation and ischemic stroke
#MMPMID26984639
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
Sci Rep
2016[Mar]; 6
(?): 23207
PMID26984639
show ga
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.
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