Correlation between polymorphism of rs5029924 in A20 promoter region and posttraumatic susceptibility to sepsis

Abstract

Objective To investigate relationship of single nucleotide polymorphism (SNP)at rs5029924 locus in A20 promoter region and posttraumatic sepsis.Methods PCR-DNA sequencing was used to analyze different gene distribution at rs5029924 locus of 103 trauma patients with sepsis (Group A),120 trauma patients without sepsis (Group B) and 135 healthy peoples (control group).Relation of different genotypes at rs5029924 locus to sepsis susceptibility was analyzed.Peripheral blood cells of healthy peoples of different genotypes were stimulated using lipopolysaccharides (LPS) in vitro.Expression of A20 mRNA was measured by fluorescent quantitative PCR,expression of A20 protein by flow cytometry,and levels of TNF-α and IL-1β by ELISA method.Results Frequency of rs5029924 genotypes CC,CT and TT was respective 77.8％,20.0％ and 2.2％ in control group； 63.1％,34.0％ and 2.9％ in Group A； 83.3％,15.0％ and 1.7％ in Group B.Significantly lower frequency of CC genotype was observed in Group A when compared to Group B and control group (P ＜0.05),but no statistical differences were recorded between Group B and control group (P ＞ 0.05).CT/TT genotype increased risk coefficient of sepsis to 2.397-fold higher level when compared to CC genotype.Allele T increased prevalence of sepsis significantly as well (OR =2.056) when compared to allele C.After LPS treatment in vitro,CC genotype individuals revealed significantly higher levels of A20 mRNA and protein in peripheral blood leukocytes,but significantly lower levels of TNF-α and IL-1 β when compared to CT/TT genotype individuals.Conclusion Polymorphism of rs5029924 locus is associated with sepsis susceptibility and the reason may be that mutant genes affect promoter activity and down-regulate A20 expression,which fails to suppress inflammation. Key words: Wounds and injuries; Sepsis; Promoter regions; A20 gene