Association of the -159C/T polymorphism of the endotoxin receptor (CD14) with carotid artery disease and cardiovascular mortality in dialysis patients.
BACKGROUND
Atherosclerosis is a major problem in end-stage renal disease (ESRD) patients treated by hemodialysis and the prevalence of carotid artery disease is much higher in this group than in the general population. Repeated exposure to cytokine-inducing material, derived from dialysate, may induce a chronic inflammatory state, that could contribute to the atherosclerotic process. Endotoxin is mainly cleared from plasma by the sCD14, the soluble form of the endotoxin receptor CD14. The levels of sCD14 are associated with a polymorphism, -159 C/T, of the CD14 gene.


RESULTS
We determined the genotype for the -159 C/T polymorphism in 158 haemodialysis patients and 168 healthy controls. In patients we investigated the association between the CD14 polymorphism and carotid artery disease. With a prospective follow-up study we assessed whether the CD14 polymorphism shows any relationship with cardiovascular mortality. The polymorphic frequency was comparable between patients and controls. In patients, we found a significant difference in the prevalence of carotid artery disease between groups divided by genotype: CC 87.0%, CT 71.7%, TT 48.9% (p = 0.0093). In dialysis patients with hypertension the CC polymorphism was associated with an increased cardiovascular mortality.


CONCLUSIONS
These results demonstrate an association between the -159 C/T polymorphism of the CD14 gene and carotid artery disease in dialysis patients. We hypothesize that the low plasma clearance of endotoxin associated with the CC genotype facilitates the atherogenic action of endotoxin-derived cytokines in haemodialysis patients.
Losito
Attilio
A
Unità Operativa Nefrologia e Dialisi, Policlinico Monteluce, Perugia, Italy. atlosito@tin.it
Kalidas
Kamini
K
Santoni
Stefania
S
Errico
Rosa
R
Jeffery
Steve
S
D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D003956:Dialysis; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis
D018950:Lipopolysaccharide Receptors