Protein C genetic variation was associated with the susceptibility to acute respiratory distress syndrome in Chinese Han population

Abstract

Objective To investigate the genetic variants in the protein C (PC) and endothelial protein C receptor (EPCR) genes associated with the risk and outcome of acute respiratory distress syndrome (ARDS) patients in Chinese Han race. Methods Five tagSNPs (single nucleotide polymorphism, SNP) in the PC and EPCR genes were genotyped in patients with ARDS (n =275) and non-ARDS (n=337) in order to find the association between them in this case-control study. The SNPs were genotyped by SNPstream Beckman platform. Then, the correlation between the associated SNPs and plasma levels of activated protein C (APC) in patients with ARDS was investigated. The APC levels were measured using enzyme linked immunosorbent assay (ELISA) method. Results Association analysis revealed that two PC SNPs in perfect linkage disequilibrium, rs1799809 and rs1158867, were significantly associated with susceptibility to ARDS. T allele frequency of rs1799809 in ARDS patients was significantly higher than that in non-ARDS patients (OR=1.569, 95%CI: 1.192-2.066). And the genotype frequencies of rs1799809 were also significantly different between these two groups (P=0.007). The association remained significant after adjustment for multiple comparisons. Haplotype consisting of three SNPs in the PC gene was also associated with susceptibility to ARDS. The frequency of haplotype CCC in the ARDS samples was significantly lower than that in the non-ARDS group (P<0.01). Moreover, ARDS patients carrying rs1799809 TT genotype showed lower serum levels of APC than patients with TC and CC genotypes (Padj=0.02). However, genotype and allele analyses of EPCR did not show any significant difference between ARDS and non-ARDS patients. Conclusions These findings indicated that common genetic variation in the PC gene was significantly associated with susceptibility to ARDS in Chinese Han race. The PC genetic variation influenced plasma concentration of APC in patients with ARDS. Key words: PC; APC; EPCR; Genetic variation; SNPs; ARDS; Susceptibility; Prognosis