The common promoter polymorphism rs11666254 downregulates FPR2/ALX expression and increases risk of sepsis in patients with severe trauma.

摘要: Formyl peptide receptor 2-lipoxin (FPR2/ALX) modulates the anti-inflammatory response and therefore may be a target for treating sepsis. The purpose of this study was to investigate association between genetic variants FPR2/ALX gene sepsis after severe trauma as well further analyze functions sepsis-related polymorphisms. Three tag single-nucleotide polymorphisms (tag SNPs) that captured all common alleles across genomic region were genotyped using pyrosequencing in an initial sample consisting 275 patients with trauma. rs11666254 polymorphism, which had statistical significance, additional 371 patients, logistic regression analysis performed determine associations polymorphism susceptibility messenger RNA (mRNA) protein levels lipopolysaccharide-stimulated white blood cells determined by performing quantitative polymerase chain reactions Western blot analysis. Tumor necrosis factor (TNF)-α production measured enzyme-linked immunosorbent assay. effects promoter on transcription activity analyzed luciferase reporter Among three SNPs, only found significantly associated persisted pooled 646 showed who carried A allele higher risk developing than individuals G allele. This SNP also lower mRNA expression TNF-α from peripheral leukocyte bacterial lipoprotein stimulation. In addition, could decrease gene. is functional increases traumatic injury.