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

J Med Genet. 2007 Aug;44(8):526-31. doi: 10.1136/jmg.2006.047449. Epub 2007 Mar 16.

Abstract

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.

Publication types

  • Letter
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginase / genetics*
  • Arginase / metabolism
  • Carotid Artery, Common / pathology*
  • Case-Control Studies
  • Genotype
  • Humans
  • Myocardial Infarction / genetics*
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Tunica Intima / pathology*
  • Tunica Media / pathology*

Substances

  • Arginase