Protein C -1641A/-1654C haplotype is associated with organ dysfunction and the fatal outcome of severe sepsis in Chinese Han population.
Activation of protein C plays an important role in modulating coagulation as well as inflammation during severe sepsis. The baseline of activated protein C level in patients with severe sepsis showed interindividual variability between survivors and nonsurvivors, and the decreased level of protein C correlated with organ dysfunction and poor outcome. However, there are limited data concerning the genetic predisposition of individuals carrying two functional polymorphisms -1641A>G and -1654C>T within protein C gene to sepsis. Here we investigated the impact of these two variations on the development of severe sepsis in 240 patients with severe sepsis and 323 healthy controls using direct sequencing. After Bonferroni correction for multiple comparisons, -1641A/-1654C haplotype was significantly associated with the fatal outcome of severe sepsis (P = 0.008, OR 1.739, 95% CI 1.165-2.595), which was confirmed by multiple logistic regression analysis (P = 0.024, OR 2.090, 95% CI 1.101-3.967). Compared to patients without carrying -1641A/-1654C haplotype, the -1641A/-1654C haplotype carriers showed higher SOFAmax scores (10.3 +/- 5.2 vs. 9.0 +/- 4.5; P = 0.014) and more hepatic dysfunction (P = 0.004, OR 2.270, 95% CI 1.312-3.930). These findings suggest that protein C haplotype -1641A/-1654C is associated with organ dysfunction and is an independent risk factor for the fatal outcome of severe sepsis in Chinese Han population.
Chen
Qi Xing
QX
Key Laboratory of Multiple Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Wu
Shui Jing
SJ
Wang
Hai Hong
HH
Lv
Chen
C
Cheng
Bao Li
BL
Xie
Guo Hao
GH
Fang
Xiang Ming
XM
D000483:Alleles; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011486:Protein C / Q000235:genetics*; D018805:Sepsis / Q000235:genetics*
D011486:Protein C