The E-selectin gene polymorphism and carotid atherosclerosis in end-stage renal disease

Nephrol Dial Transplant. 2006 Jul;21(7):1921-6. doi: 10.1093/ndt/gfl115. Epub 2006 Mar 22.

Abstract

Background: E-selectin is a cell surface glycoprotein that mediates the adhesion of leucocytes to vessels endothelium, an important early step in the atherosclerotic process. End-stage renal disease (ESRD) is a highly atherogenic disease but it is unknown whether genetic polymorphism(s) in the E-selectin gene plays a role in the severity of arterial damage in this condition. Method. In this study, we tested whether the Leu554Phe variant in the E-selectin gene is linked to carotid atherosclerosis in 134 well-characterized ESRD patients. The frequency of this polymorphism was also measured in a population sample of the same geographical area.

Results: A total of 84% patients had the CC genotype, 13% had the CT genotype, 3% had the TT genotype and this distribution did not differ from that in the control population. Intima-media thickness (IMT) (P = 0.01) and cross-sectional area (P = 0.02) were significantly higher in patients with the T-allele than in those without this allele. Furthermore, the degree of carotid stenosis was significantly higher (P = 0.02) in patients with T-allele than in CC patients. On multivariate analyses including the traditional and non-traditional risk factors, the Leu554Phe polymorphism was confirmed as an independent correlate of IMT (P = 0.02), cross-sectional area (P = 0.03) and carotid stenosis (P = 0.02).

Conclusion: In ESRD, the Leu554Phe polymorphism of E-selectin gene is associated with the severity of carotid atherosclerosis, suggesting that genetically-determined alterations in the E-selectin molecule may render ESRD patients with this gene variant particularly susceptible to the detrimental effects of inflammation on the arterial wall.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Atherosclerosis / genetics
  • Carotid Artery Diseases / complications*
  • Carotid Artery Diseases / genetics*
  • Carotid Stenosis / complications
  • Carotid Stenosis / genetics
  • Case-Control Studies
  • E-Selectin / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Genotype
  • Humans
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / genetics*
  • Male
  • Middle Aged
  • Models, Genetic
  • Polymorphism, Genetic*
  • Regression Analysis
  • Risk Factors

Substances

  • E-Selectin