Background: Recently, it was suggested that arginase (ARG)1 plays an important role in atherogenesis. However, because of its complex functions depending on vascular cell type, its impact on atherogenesis remains unclear.
Objective: To evaluate the association between ARG1 polymorphisms and phenotypes related to atherosclerosis.
Methods: Among 10 ARG1 polymorphisms selected from databases, 4 single-nucleotide polymorphisms (rs2781666; rs2781667; rs2781668; rs17599586) were tested for association with myocardial infarction (MI) in a case–control study (350 cases vs 581 controls), and with common carotid artery (CCA) intima–media thickness (CCA-IMT) in an independent sample of 963 subjects (Etude du Vieillissement Artériel (EVA) study).
Results: The genotype distribution of the rs2781666 G/T polymorphism differed significantly between MI cases and controls (p = 0.005), and the risk of MI was consistently increased for both GT heterozygotes (OR (95% CI) 1.5 (1.1 to 2.0)) and TT homozygotes (OR (95% CI) 2.2 (1.1 to 4.4)). In the EVA study, the rs2781666 polymorphism was also associated with an increase in CCA-IMT (p = 0.010), a surrogate marker of MI.
Conclusions: The ARG1 rs2781666 polymorphism was consistently associated with MI and an increased CCA-IMT. These findings reinforce the hypothesis of a significant role of ARG1 in vascular pathophysiology.
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- ARG, arginase
- CAD, coronary artery disease
- CCA, common carotid artery
- CCA-IMT, CCA intima–media thickness
- DBP, diastolic blood pressure
- EUROASPIRE, European Action on Secondary Prevention by Intervention to Reduce Events
- EVA, Etude du Vieillissement Artériel
- LD, linkage disequilibrium
- MI, myocardial infarction
- NO, nitric oxide
- NOS, NO synthase
- SBP, systolic blood pressure
- SNP, single-nucleotide polymorphism
- VSMC, vascular smooth muscle cells
Competing interests: None.
Published Online First 16 March 2007
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