Endothelial protein C receptor 1651C/G polymorphism and soluble endothelial protein C receptor levels in women with idiopathic recurrent miscarriage.
High levels of soluble endothelial protein C receptor (EPCR) induce coagulation dysfunction by inhibiting protein C activation, and activated protein C (APC) activity. We tested whether EPCR 1651C/G promoter variant and changes in plasma soluble EPCR levels are risk factors for idiopathic recurrent spontaneous miscarriage (RSM). A case-control study involving 283 RSM cases and 380 age and BMI-matched control women. EPCR 1651C/G genotyping was performed by PCR-RFLP method. Plasma-soluble EPCR levels were measured with ELISA. The 1651G allele frequency and C/G genotype were significantly higher in RSM cases than controls; none of the cases or control participants was a 1651G/G homozygote. Lower soluble EPCR levels were seen in RSM cases compared to controls, and higher soluble EPCR levels were seen in 1651C/G compared to 1651C/C carriers in cases and controls. Lower soluble EPCR levels were seen in cases, both in 1651C/C (P = 0.0046) and 1651C/G (P = 0.0032) genotype carriers. Multivariate analysis demonstrated strong association of EPCR 1651C/G [P = 0.011; adjusted odds ratio (aOR) (95% confidence interval [CI] = 3.13 (1.31-7.60)], but not soluble EPCR plasma levels [P = 0.067; aOR (95% CI) = 1.01 (1.00-1.10)], with increased RSM risk. In addition, smoking was independently associated with increased RSM risk [P = 0.002; aOR (95% CI) = 2.86 (1.48-5.52)]. EPCR 1651C/G polymorphism and elevated soluble EPCR levels but low soluble EPCR levels increase the risk of idiopathic RSM. Replication studies on other racial groups, and other EPCR gene variants, are warranted.
Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Maryam
M
Dendana
Safia
S
Messaoudi
Sondes
S
Hizem
Khaled B
KB
Jazia
Wassim Y
WY
Almawi
Jean-Christophe
JC
Gris
Touhami
T
Mahjoub
D000026:Abortion, Habitual / Q000097:blood / Q000235:genetics* / Q000276:immunology; D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D000074283:Endothelial Protein C Receptor; D005260:Female; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood / Q000235:genetics* / Q000276:immunology; D011486:Protein C / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011486:Protein C; D011956:Receptors, Cell Surface