Presence of the apolipoprotein E-ε4 allele is associated with an increased risk of sepsis progression

Abstract

Growing evidence indicated that single nucleotide polymorphisms (SNPs) in the apolipoprotein E (APOE) gene are related to increase the risk of many inflammatory-related diseases. However, few genetic studies have associated the APOE gene polymorphism with sepsis. This study was to investigate the clinical relevance of the APOE gene polymorphism in the onset and progression of sepsis. A multicenter case–control association study with a large sample size (601 septic patients and 699 healthy individuals) was conducted. Clinical data showed that the APOEε4 allele was overrepresented among all patients with septic shock (p = 0.031) compared with sepsis subtype, suggesting that APOEε4 allele may associated with increased susceptibility to the progression of sepsis. Moreover, the APOE mRNA levels decreased after lipopolysaccharide (LPS) stimulation in cells in culture. Then 21 healthy individuals to extract PBMC for genotype grouping (APOE4+ group 8; APOE4− group 13) was selected to evaluate the effect on APOE level, and results showed that the expression level of APOE in APOE4+ group and APOE4− group did not differ in mRNA levels after an LPS challenge, but the protein levels in APOE4+ group decreased slower than that in APOE4− group, and this process was accompanied by the upregulation of proinflammatory cytokines. These results provide evidence that the APOEε4 allele might be associated with the development of sepsis and a potential risk factor that can be used in the prognosis of sepsis.