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

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)
(P¼0.01) and cross-sectional area (P¼0.02) were
significantly higher in patients with the T-allele than
in those without this allele. Furthermore, the degree
of carotid stenosis was significantly higher (P¼0.02)
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 (P¼0.02), cross-sectional area (P¼0.03)
and carotid stenosis (P¼0.02).
Conclusion. In ESRD, the Leu554Phe polymorphism
of E-selectin gene is associated with the severity of
carotid atherosclerosis, suggesting that geneticallydetermined
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.