Promoter Genetic Polymorphism Of PROC Genes In Patients With Sepsis And Thrombocytopenia In Sepsis

ObjectiveImpairment of the protein C (PROC) anticoagulation pathway can contribute tothrombosis and is associated with substantial morbidity and mortality due to sepsis. Inpatients with sepsis, low PROC levels have been correlated with increased sepsisseverity and poor outcome. Three polymorphisms in the promoter region ofPROC(-1654T/C,-1641A/G and-1476A/T) have been shown to affect the PROClevels. The aim of this case-control study was to identify four single nucleotidepolymorphisms (SNPs)(-1654T/C,-1641A/G,-1476A/T and-839A/G) and/orhaplotypes in the promoter of the PROC gene in400individuals. At the same time toidentify the relationship between two single nucleotide polymorphisms(（rs1799808(-1654T/C) and rs1799809(-1641A/G)) in the promotor of the PROCgene with total serum platelet level in sepsis patients.MethodsA total of187patients with pneumonia-induced sepsis and213age-andsex-matched healthy volunteers participated in our study from July2012to July2013in the intensive care unit (ICU) at the Third Affiliated Hospital of Guangzhou MedicalUniversity (Guangzhou, China). Patient clinical information was collected. Clinicalpathology was assessed in subgroups defined based on clinical criteria, APACHE II(acute physiology and chronic health evaluation) and SOFA (sepsis-related organfailure assessment) scores and discharge rate. Four single nucleotide polymorphisms(SNPs)(-1654T/C,-1641A/G,-1476A/T and-839A/G) and/or haplotypes in the promoter of the PROC gene were analyzed by polymerase chain reaction (PCR) andsequence analysis in both sepsis patients and healthy controls. Pearson’s chi-squaretest or Fisher’s exact test were used to analyze the distribution of the SNPs, and theprobability values (P values), odds ratios (OR) and95%confidence intervals (CIs)were calculated.Results1) Neither the genotype frequencies nor the allele frequencies of the polymorphismsfor PROC gene were significantly associated with the outcome of severe sepsis.The CGT haplotype was significantly associated with sepsis (P<0.05).2) Genotype distribution, allele frequencies and haplotypes of sepsis patients werecomparable to thrombocytopenia group and the normal group. Notable diversitywas found the frequency of alleles-1654T in the thrombocytopenia group washigher than the normal group (P=0.03)，and the frequency of haplotype TA in thethrombocytopenia group being significantly higher than that in normal group t(P=0.04).ConclusionOur results suggest that PROC SNPs are associated with sepsis and plateletconcentration in the process of sepsis.