Cytokine polymorphisms associated with carotid intima-media thickness in stroke patients

Stroke. 2006 Jul;37(7):1691-6. doi: 10.1161/01.STR.0000226565.76113.6c. Epub 2006 Jun 1.

Abstract

Background and purpose: Carotid intima-media thickness (IMT) reflects generalized atherosclerosis and is predictive of future vascular events. Evidence exists that carotid IMT is heritable, and genetic studies can provide clues in the pathogenesis of atherosclerosis.

Methods: We recruited 470 white ischemic stroke patients, measured common carotid artery (CCA) IMT, and analyzed 54 polymorphisms with suspected roles in atherosclerosis.

Results: Among the polymorphisms tested, the angiotensin-converting enzyme insertion/deletion, osteopontin (OPN) T-443C, monocyte chemoattractant protein-1 (MCP-1) G-927C, and MCP-1 A-2578G polymorphisms were associated with CCA-IMT in age-gender-adjusted analysis. In multivariate analysis, the association between the OPN and MCP-1 polymorphisms remained significant. The OPN-443C allele was associated with increased IMT in the dominant model (0.053 mm for the TC and CC genotypes; P=0.001). The MCP-1-927C allele was associated with increased IMT in the additive model (0.040 mm for each C allele; P=0.001), and the MCP-1-2578 G allele was associated with decreased IMT in the recessive model (0.088 mm for the GG genotype; P=0.002).

Conclusions: The OPN and MCP-1 genes, coding for 2 cytokines with known roles in atherosclerosis, may contribute to increased carotid IMT and warrant further study.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Blood Proteins / genetics
  • Brain Ischemia / genetics
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / genetics*
  • Carotid Artery Diseases / pathology
  • Carotid Artery, Common / diagnostic imaging
  • Carotid Artery, Common / ultrastructure*
  • Chemokine CCL2 / genetics*
  • Chemokine CCL2 / physiology
  • Enzymes / genetics
  • Female
  • France / epidemiology
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Osteopontin
  • Peptidyl-Dipeptidase A / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Single-Stranded Conformational
  • Risk Factors
  • Sialoglycoproteins / genetics*
  • Sialoglycoproteins / physiology
  • Tunica Intima / diagnostic imaging
  • Tunica Intima / ultrastructure*
  • Tunica Media / diagnostic imaging
  • Tunica Media / ultrastructure*
  • Ultrasonography
  • White People / genetics

Substances

  • Blood Proteins
  • CCL2 protein, human
  • Chemokine CCL2
  • Enzymes
  • SPP1 protein, human
  • Sialoglycoproteins
  • Osteopontin
  • Peptidyl-Dipeptidase A