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) (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).


CONCLUSIONS
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.
Testa
Alessandra
A
CNR-IBIM, National Research Council-Institute of Biomedicine, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.
Benedetto
Francesco A
FA
Spoto
Belinda
B
Pisano
Anna
A
Tripepi
Giovanni
G
Mallamaci
Francesca
F
Malatino
Lorenzo S
LS
Zoccali
Carmine
C
D000368:Aged; D000483:Alleles; D050197:Atherosclerosis / Q000235:genetics; D002340:Carotid Artery Diseases / Q000150:complications* / Q000235:genetics*; D016893:Carotid Stenosis / Q000150:complications / Q000235:genetics; D016022:Case-Control Studies; D019040:E-Selectin / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors
D019040:E-Selectin