Human genetics
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Randomized Controlled Trial Comparative Study
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. ⋯ 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.