Circulating Endothelial Cell Protein C Receptor: Endothelial Regulation and Cumulative Impact of Gender and A3 Haplotype

Guitton, Christophe; Gérard, Nathalie; Quillard, Thibaut; Charreau, Béatrice

doi:10.1159/000322582

Cited by 10 publications

(10 citation statements)

References 78 publications

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“…In previous studies, sEPCR levels in septic patients were found to be significantly higher [12,26], similar [27], or even lower [28] than in healthy volunteers. These results confirm our previous data indicating that gender was a critical parameter determining basal levels of sEPCR [29]. Moreover, we observed here that gender ratio may be another key factor affecting D1 sEPCR in septic patients.…”

Section: Discussionsupporting

confidence: 93%

Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis

et al. 2011

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Section: Discussionsupporting

confidence: 93%

Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis

et al. 2011

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“…We confirmed recent data [31] demonstrating that gender strongly correlates with sEPCR levels, with higher circulating sEPCR levels observed in males. We found a strong association between diabetes and sEPCR levels.…”

Section: Discussionsupporting

confidence: 92%

“…Further studies are needed to investigate the relationship between EPCR membrane expression and its circulating form. Indeed, a recent study reported that TNFα causes a rapid down-regulation of membrane associated EPCR expression without markedly affecting the spontaneous release of sEPCR by arterial endothelial cells [31]. …”

Section: Discussionmentioning

confidence: 99%

Association of soluble endothelial protein C receptor plasma levels and PROCR rs867186 with cardiovascular risk factors and cardiovascular events in coronary artery disease patients: The Athero Gene Study

Kallel

Cohen

Blankenberg³

et al. 2012

BMC Med Genet

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BackgroundBlood coagulation is an essential determinant of coronary artery disease (CAD). Soluble Endothelial Protein C Receptor (sEPCR) may be a biomarker of a hypercoagulable state. We prospectively investigated the relationship between plasma sEPCR levels and the risk of cardiovascular events (CVE).MethodsWe measured baseline sEPCR levels in 1673 individuals with CAD (521 with acute coronary syndrome [ACS] and 1152 with stable angina pectoris [SAP]) from the AtheroGene cohort. During a median follow up of 3.7 years, 136 individuals had a CVE. In addition, 891 of these CAD patients were genotyped for the PROCR rs867186 (Ser219Gly) variant.ResultsAt baseline, sEPCR levels were similar in individuals with ACS and SAP (median: 111 vs. 115 ng/mL respectively; p=0.20). Increased sEPCR levels were found to be associated with several cardiovascular risk factors including gender (p=0.006), soluble Tissue Factor levels (p=0.0001), diabetes (p=0.0005), and factors reflecting impaired renal function such as creatinine and cystatin C (p<0.0001). sEPCR levels were not significantly associated with the risk of CVE (median: 110 and 114 ng/mL in individuals with and without future CVE respectively; p=0.68). The rs867186 variant was found to explain 59% of sEPCR levels variability (p<10-200) but did not associate with CVE risk.ConclusionOur findings show that in patients with CAD, circulating sEPCR levels are related to classical cardiovascular risk factors and renal impairment but are not related to long-term incidence of CVE.

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“…Four haplotypes are defined by the SNPs: H1–H4 [ 18 – 20 ]. The H3 haplotype has been associated with increased plasma sEPCR levels [ 19 , 22 , 23 ] and has been suggested to be a risk factor for venous thrombosis [ 19 , 21 ], although other studies could not confirm this [ 18 , 20 ]. Contrary to H3, the H1 haplotype has been associated with elevated APC plasma concentration and a protective effect against venous thrombosis [ 20 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania

Hansson

Turner

Møller

et al. 2015

Malar J

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BackgroundEndothelial protein C receptor (EPCR) was recently identified as a key receptor for Plasmodium falciparum erythrocyte membrane protein 1 mediating sequestration of P. falciparum-infected erythrocytes in patients suffering from severe malaria. Soluble EPCR (sEPCR) inhibits binding of P. falciparum to EPCR in vitro and increased levels of sEPCR have been associated with the H3 haplotype of the EPCR encoding PROCR gene. It has been hypothesized that elevated sEPCR levels, possibly linked to the PROCR H3 genetic variant, may confer protection against severe forms of malaria. This study determined the frequencies of PROCR haplotypes H1–4 and plasma levels of sEPCR in a Tanzanian study population to investigate a possible association with severe malaria. MethodsStudy participants were children under 5 years of age admitted at the Korogwe District Hospital (N = 143), and diagnosed as having severe malaria (N = 52; including cerebral malaria N = 17), uncomplicated malaria (N = 24), or an infection other than malaria (N = 67). In addition, blood samples from 71 children living in nearby villages were included. The SNPs defining the haplotypes of PROCR gene were determined by post-PCR ligation detection reaction-fluorescent microsphere assay.ResultsIndividuals carrying at least one H3 allele had significantly higher levels of sEPCR than individuals with no H3 alleles (P < 0.001). No difference in the frequency of H3 was found between the non-malaria patients, malaria patients or the village population (P > 0.1). Plasma levels of sEPCR differed between these three groups, with higher sEPCR levels in the village population compared to the hospitalized patients (P < 0.001) and higher levels in malaria patients compared to non-malaria patients (P = 0.001). However, no differences were found in the distribution of H3 (P = 0.2) or levels of sEPCR (P = 0.8) between patients diagnosed with severe and uncomplicated malaria.ConclusionFrequencies of SNPs determining PROCR haplotypes were in concordance with other African studies. The PROCR H3 allele was associated with higher levels of sEPCR, confirming earlier findings, however, in this Tanzanian population; neither PROCR haplotype nor level of sEPCR was associated with severe malaria, however, larger studies are needed to confirm these findings.

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Circulating Endothelial Cell Protein C Receptor: Endothelial Regulation and Cumulative Impact of Gender and A3 Haplotype

Cited by 10 publications

References 78 publications

Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis

Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis

Association of soluble endothelial protein C receptor plasma levels and PROCR rs867186 with cardiovascular risk factors and cardiovascular events in coronary artery disease patients: The Athero Gene Study

Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania

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