The sex-specific association of Met62Ile gene polymorphism in P-selectin glycoprotein ligand (PSGL-1) with carotid plaque presence: preliminary study

Mol Biol Rep. 2012 Jun;39(6):6479-85. doi: 10.1007/s11033-012-1475-5. Epub 2012 Feb 4.

Abstract

Atherosclerosis is known as an inflammatory disease in which a recruitment of leukocytes to the endothelium wall represents a preliminary step of the initiation and the development of disease. The P-selectin glycoprotein ligand (PSGL-1) seems to be the major molecule mediating leukocyte-endothelium interactions and leukocyte rolling on stimulated endothelium. There are limited number of studies reporting on association of Met62Ile SNP in PSGL-1 gene and the risk for atherosclerosis. The aim of this study was to analyze possible association of this polymorphism with an advanced carotid atherosclerosis and biochemical markers of inflammation and haemostasis. The 275 patients consecutively admitted for carotid endarterectomy with stenosis >70% and 256 controls of the same ethnic origin were included in the study. The Met62Ile genotypes were determined by PCR RFLP. The Ile/Ile homozygotes had significantly higher CRP compared to the other genotypes in patients. Female patients had Ile allele dose-dependent association with the carotid plaque presence (Met/Met vs. Met/Ile vs. Ile/Ile; OR 1, OR 2.02, CI 1.0-4.08, OR 4.08, CI 1.0-16.81, respectively, p = 0.04). Our results suggest the impact of PSGL-1 Met62Ile polymorphism on inflammation in advanced atherosclerosis. We observed the sex-differential association of Met62Ile with advanced carotid atherosclerosis. Studies in larger and different populations should validate and further examine the suggested role of genetic variations in PSGL-1 with atherosclerosis and thrombosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution
  • Atherosclerosis / blood
  • Atherosclerosis / genetics*
  • Blood Proteins / metabolism
  • Carotid Stenosis / blood
  • Carotid Stenosis / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Humans
  • Male
  • Membrane Glycoproteins / blood
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Plaque, Atherosclerotic / blood
  • Plaque, Atherosclerotic / genetics
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA
  • Sex Factors

Substances

  • Blood Proteins
  • Membrane Glycoproteins
  • P-selectin ligand protein