Association of arginase 1 gene polymorphisms with the risk of myocardial infarction and common carotid intima media thickness.

Abstract

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. To evaluate the association between ARG1 polymorphisms and phenotypes related to atherosclerosis. 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). 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. 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.