RGD Reference Report - Association of the -159C/T polymorphism of the endotoxin receptor (CD14) with carotid artery disease and cardiovascular mortality in dialysis patients.

General

Association of the -159C/T polymorphism of the endotoxin receptor (CD14) with carotid artery disease and cardiovascular mortality in dialysis patients.
Authors:	Losito, A Kalidas, K Santoni, S Errico, R Jeffery, S
Citation:	Losito A, etal., Blood Purif. 2005;23(2):128-33. Epub 2005 Jan 6.
RGD ID:	7204441
Pubmed:	PMID:15640605 (View Abstract at PubMed)
DOI:	DOI:10.1159/000083207 (Journal Full-text)
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. METHODS AND 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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
carotid artery disease	susceptibility	IAGP		7204441	associated with Kidney Failure more ...	RGD
carotid artery disease	susceptibility	ISO	CD14 (Homo sapiens)	7204441; 7204441	associated with Kidney Failure more ...	RGD

Objects Annotated

Genes (Rattus norvegicus)

Cd14 (CD14 molecule)

Genes (Mus musculus)

Cd14 (CD14 antigen)

Genes (Homo sapiens)

CD14 (CD14 molecule)

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Association of the -159C/T polymorphism of the endotoxin receptor (CD14) with carotid artery disease and cardiovascular mortality in dialysis patients.