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Background  Formyl peptide receptor 2-lipoxin receptor (FPR2/ALX) modulates the anti-inflammatory response and therefore may be a target for treating sepsis. The purpose of this study was to investigate the association between genetic variants of the  FPR2/ALX  gene and sepsis after severe trauma as well as to further analyze the functions of sepsis-related genetic polymorphisms.    Methods  Three tag single-nucleotide polymorphisms (tag SNPs) that captured all common alleles across the  FPR2/ALX  genomic region were genotyped using pyrosequencing in an initial sample consisting of 275 patients with severe trauma. The rs11666254 polymorphism, which had statistical significance, was genotyped in an additional 371 patients, and logistic regression analysis was performed to determine associations between the  FPR2/ALX  gene polymorphism and sepsis susceptibility after severe trauma. The messenger RNA (mRNA) and protein levels of FPR2/ALX in the lipopolysaccharide-stimulated white blood cells of trauma patients were determined by performing quantitative polymerase chain reactions and Western blot analysis. Tumor necrosis factor (TNF)-α production was measured by enzyme-linked immunosorbent assay. The effects of the promoter polymorphism rs11666254 on the transcription activity of  FPR2/ALX  were analyzed using a luciferase reporter assay.    Results  Among the three tag SNPs, only the rs11666254 polymorphism was found to be significantly associated with sepsis in trauma patients, and this association persisted after a pooled analysis of all 646 trauma patients, which showed that patients who carried the A allele of rs11666254 had a significantly higher risk of developing sepsis than individuals who carried the G allele. This SNP was also significantly associated with lower FPR2/ALX mRNA and protein expression as well as higher TNF-α production from the peripheral blood leukocyte response to bacterial lipoprotein stimulation. In addition, the rs11666254 polymorphism could significantly decrease the promoter activity of the  FPR2/ALX  gene.    Conclusions  The rs11666254 polymorphism in the  FPR2/ALX  gene is a functional SNP that increases sepsis susceptibility in patients after traumatic injury.    Electronic supplementary material  The online version of this article (doi:10.1186/s13054-017-1757-3) contains supplementary material, which is available to authorized users.

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