|(A;A)||0||normal risk for VTE|
|(A;G)||EPCR H3 haplotype; reduced or increased risk of VTE?|
|(G;G)||EPCR H3 diplotype; reduced or increased risk of VTE?|
rs867186 is a SNP that can indicate haplotype H3 of the EPCR gene. The protein product of the EPCR gene activates a part of the anticoagulation pathway. While the rs867186(A) allele could indicate haplotypes H1, H2 or H4, the rs867186(G) allele distinctly tags (identifies) the H3 haplotype.[PMID 17849044]
While most groups studying EPCR H3 agree that it leads to increased soluble EPCR, and thus should theoretically lead to reduced risk for venous thromboembolism, different groups come to different conclusions about the effect in the populations each studies. Two find no association [PMID 15304035, PMID 15116250] while one finds that the H3 haplotype (and thus rs867186(G)) actually increases the risk of venous thromboembolism (VTE), with an odds ratio of 1.80, p=0.004.[PMID 14576048]
|Trait||Plasma coagulation factors|
|Title||Novel Associations of Multiple Genetic Loci With Plasma Levels of Factor VII, Factor VIII, and von Willebrand Factor. The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium|
|Odds Ratio||None None|
|Title||Genome-wide association study identifies novel loci for plasma levels of protein C: the ARIC study|
|Odds Ratio||0.47 [0.44-0.50] ug/ml increase|
|Title||Genetic predictors of fibrin D-dimer levels in healthy adults.|
|Odds Ratio||0.0484 [NR] % increase|
|Title||A genome-wide association study of the Protein C anticoagulant pathway.|
|Odds Ratio||0.8450 None|
[PMID 22443383] Genome wide association study for plasma levels of natural anticoagulant inhibitors and protein C anticoagulant pathway: the MARTHA project
[PMID 16846490] Lemierre's syndrome and genetic polymorphisms: a case report.
[PMID 18680534] PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study.
[PMID 18947391] Hemostasis and ageing.
[PMID 22251481] The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies.
[PMID 23136988] 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 AtheroGene Study
[PMID 24635948] Association of the endothelial protein C receptor (PROCR) rs867186-G allele with protection from severe malaria
[PMID 25376901] Genetic Markers Associated With Plasma Protein C Level in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study
[PMID 24816905] Single nucleotide variants in the protein C pathway and mortality in dialysis patients
[PMID 27882376] Plasma levels of the anti-coagulation protein C and the risk of ischaemic heart disease. A Mendelian randomisation study.
[PMID 28415941] Endothelial protein C receptor polymorphisms and risk of sepsis in a Chinese population.
[PMID 28530674] Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms.
[PMID 29112333] Associations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk.