title: Endothelial protein C receptor polymorphisms and risk of severe sepsis in critically ill patients.
abstract: OBJECTIVE
  Endothelial protein C receptor (EPCR) is expressed mainly in endothelial cells and is involved in regulation of the cytoprotective and anticoagulant pathways of protein C. We assessed whether haplotypes in the EPCR gene modify the risk of severe sepsis and/or septic shock (SS/SS) development in critically ill patients.
  
  
  METHODS
  Three polymorphisms in the EPCR gene were genotyped in 389 Caucasian critically ill patients, hospitalized in the intensive care units of two major hospitals in Athens, Greece. Multivariate logistic regression analysis controlling for age, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, sex, and diagnosis was performed to determine the effect of haplotypes H1 and H3 in the EPCR gene on the development of SS/SS.
  
  
  RESULTS
  H2 carriers versus all other genotypes combined had a nonsignificant excess of SS/SS (p = 0.087). SS/SS occurred in 38.8% of critically ill patients carrying minor alleles belonging to both H1 and H3 haplotypes, in 58.0% of H1 carriers, 64.3% of H3 carriers, and 65.2% of patients carrying all common alleles (H2). Compared with H2 carriers, the odds ratios (OR) for developing SS/SS were 0.34 [95% confidence interval (CI) 0.16-0.76, p = 0.008] for simultaneous H1 and H3 carriers, 0.65 (95% CI 0.37-1.13, p = 0.123) for H1 carriers, and 0.82 (95 % CI 0.39-1.70, p = 0.590) for H3 carriers.
  
  
  CONCLUSIONS
  Our results indicate that simultaneous carriers of minor alleles belonging to both the H1 and H3 haplotypes may be at reduced risk of developing SS/SS in this cohort of critically ill patients.
authors.affiliation: 1st Department of Critical Care Medicine and Pulmonary Services, GP Livanos and M Simou Laboratories, Medical School of Athens University, Evangelismos Hospital, Athens, Greece, alvass75@gmail.com.
authors.forename: Alice G
authors.initials: AG
authors.lastname: Vassiliou
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Maniatis
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kotanidou
authors.forename: Marina
authors.initials: M
authors.lastname: Kallergi
authors.forename: Foteini S
authors.initials: FS
authors.lastname: Karystinaki
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Letsiou
authors.forename: Constantinos
authors.initials: C
authors.lastname: Glynos
authors.forename: Petros
authors.initials: P
authors.lastname: Kopterides
authors.forename: Dimitra
authors.initials: D
authors.lastname: Vassiliadi
authors.forename: Nikitas
authors.initials: N
authors.lastname: Nikitas
authors.forename: Ioanna
authors.initials: I
authors.lastname: Dimopoulou
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Orfanos
mesh_terms: D018806:APACHE; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D016638:Critical Illness; D000074283:Endothelial Protein C Receptor; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006115:Greece; D006239:Haplotypes; D006801:Humans; D007362:Intensive Care Units; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011486:Protein C / Q000235:genetics* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology; D018570:Risk Assessment; D018805:Sepsis / Q000235:genetics; D012772:Shock, Septic / Q000235:genetics*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011486:Protein C; D011956:Receptors, Cell Surface