PMID- 17849054
OWN - NLM
STAT- MEDLINE
DCOM- 20071101
LR  - 20181201
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 98
IP  - 3
DP  - 2007 Sep
TI  - Effects of toll-like receptor-4 gene polymorphisms on soluble P-selectin and von 
      Willebrand factor levels in hypercholesterolemic patients.
PG  - 642-6
AB  - Toll-like receptor-4 (TLR-4) gene polymorphisms have been associated with a lower 
      risk of atherosclerosis. High levels of soluble P-selectin (sP-selectin) and von 
      Willebrand factor predict an increased risk for cardiovascular events and 
      correlate to atherosclerotic risk factors. The relationship between these markers 
      and TLR-4 gene polymorphisms was evaluated in a cohort of consecutive 
      hypercholesterolemic outpatients. TLR-4 gene polymorphisms were detected in 48 
      out of 330 (14%) patients with hypercholesterolemia. Lipid and inflammatory 
      markers, sP-selectin and von Willebrand were evaluated in carriers and in 96 
      (ratio 2:1 to cases) age- and sex-matched TLR-4 wild-type patients randomly 
      selected from the same population. A cohort of normocholesterolemic outpatients 
      (n = 262) served as the control group. sP-selectin was sensibly lower in carriers 
      of TLR-4 variants as compared to wild-types and controls (89 ng/ml vs. 162 ng/ml 
      and 163 ng/dl, respectively, p = 0.0001). Similarly, carriers showed lower von 
      Willebrand factor values (683 mU/ml) than wild-types (910 mU/ml; p = 0.001). In 
      multivariate analysis, TLR-4 gene polymorphisms were positively associated with 
      sP-selectin, whereas the relationship with von Willebrand factor was no longer 
      significant. HMG-CoA reductase inhibitors reduced sP-selectin and von Willebrand 
      factor levels independently of TLR-4 gene variants. Plasma concentrations of 
      these markers, however, remained lower in carriers of TLR-4 gene polymorphisms 
      even after cholesterol lowering. In conclusion, carriership of Asp299 and 
      Thr399Ile TLR-4 gene polymorphisms is associated with lower levels of sP-selectin 
      and von Willebrand factor among hypercholesterolemic patients. While the 
      underlying mechanisms remain to be investigated, such an association may indicate 
      a protective effect of TLR-4 variants for atherosclerosis.
FAU - Di Nisio, Marcello
AU  - Di Nisio M
AD  - Department of Medicine and Aging, Aging Research Center, Ce.S.I., G. D'Annunzio 
      University Foundation, Chieti-Pescara, Italy.
FAU - Di Febbo, Concetta
AU  - Di Febbo C
FAU - Moretta, Valeria
AU  - Moretta V
FAU - Guglielmi, Maria Domenica
AU  - Guglielmi MD
FAU - Stuppia, Liborio
AU  - Stuppia L
FAU - Cuccurullo, Franco
AU  - Cuccurullo F
FAU - Porreca, Ettore
AU  - Porreca E
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Lipids)
RN  - 0 (P-Selectin)
RN  - 0 (Pyrroles)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (von Willebrand Factor)
RN  - A0JWA85V8F (Atorvastatin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Atherosclerosis/blood/*genetics/prevention & control
MH  - Atorvastatin
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Cross-Sectional Studies
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Heptanoic Acids/*therapeutic use
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use
MH  - Hypercholesterolemia/blood/complications/drug therapy/*genetics
MH  - Lipids/blood
MH  - Male
MH  - Middle Aged
MH  - P-Selectin/*blood
MH  - Phenotype
MH  - *Polymorphism, Genetic
MH  - Pyrroles/*therapeutic use
MH  - Risk Factors
MH  - Toll-Like Receptor 4/*genetics
MH  - Treatment Outcome
MH  - von Willebrand Factor/*metabolism
EDAT- 2007/09/13 09:00
MHDA- 2007/11/02 09:00
CRDT- 2007/09/13 09:00
PHST- 2007/09/13 09:00 [pubmed]
PHST- 2007/11/02 09:00 [medline]
PHST- 2007/09/13 09:00 [entrez]
AID - 07090642 [pii]
PST - ppublish
SO  - Thromb Haemost. 2007 Sep;98(3):642-6.