The influence of the CD14 SNP rs2569190 on the course of illness of patients with sepsis

The CD14-Receptor plays a pivotal role in the recognition of pathogenic germs by the innate immune system. After the recognition of pathogenic germs the CD14-Receptor activates an immune response resulting in a release of proinflammatory cytokines. Therefore we suggested to prove the influence caused by genetic polymorphisms of CD14 on the immune response. By the results of other studies there was a heavy evidence for influencing the innate immune system by the CD14 SNP rs2569190. While the C-allele seems to increase the risk of developing an infection, the T-allele is associated with an improved survival of critical ill patients on the intensive care unit. According to earlier results, which has shown that there could be an influence caused by the SNP rs2569190 on sepsis, and because sepsis is a heavy complication of an infection, we decided to prove the CD14 SNP rs2569190 into a group of patients with sepsis. The aim of our study was to show if the CD14 SNP rs2569190 is associated with the mortality risk, the heaviness of sepsis or an influence on the organic function in patients with sepsis. From April 2012 till June 2014 we examined 417 patients of totally three intensive care units of the UMG. All patients fulfilled the ACCP/SCCM-Consensus-Conference-Criteria and consented to our study. We collected clinical data daily for a period of 30 days and took blood of every patient for DNA-extraction and analyzing the genotype. The observed genotypes were in Hardy-Weinberg equilibrium with a minor allele frequency of 0,45. We could show that there is a significant difference between the genotypes according to the mortality risk. While TT-genotypes after 30 days have a mortality risk of 13%, patients carrying the C-allele have a mortality risk of 23% (p=0,0490). The CD14 rs2569190 C allele is also remained a significant covariate for 30-day mortality risk in a multivariate analysis (hazard ratio, 2.11; p = 0.0282). However this significant difference disappears after a period of 90 days. On the one hand this could mean that the CD14 SNP rs2569190 is associated with the short-term survival, but on the other hand that there is no evidence for the long-term survival. Therefore the increased release of proinflammatory cytokines by T-allele carriers, which results in a stronger immune response with an associated important role in the first period of a sepsis, could be a possible explanation. Furthermore in our study there was no influence caused by the CD14 SNP rs2569190 on the heaviness of sepsis, because there was no significant difference in the distribution of the subtypes sepsis, severe sepsis and septic shock. Also there was no significant correlation between the APACHE II and SOFA Scores, the value of inflammatory blood markers, the length of the stay on the intensive care unit or days without organ support therapy. But we could find a significant correlation between the CD14 SNP rs2569190 and the SOFA-Central nervous system score. The SOFA-Central nervous system score of TT-carriers was 0,3 points lower compared to carriers of the C-allele, while there was no significant difference in the other organ specific Subscores. The decreased concentration of sCD14 caused by the SNP effects an increased concentration of LPS, which perhaps has a negative influence on cognitive functions and could be a possible explanation. However, this finding has to be interpreted carefully because the SOFA-Central nervous system score can be affected by the sedative medications given to critically ill patients, which is a potential confounding factor. In conclusion, this is the first study to show a beneficial association of the CD14 rs2569190 TT genotype with short-term survival (30-day) in a cohort of sepsis patients of exclusively western European descent.2018-08-2