Association Between Gene Polymorphism Of Platelet-activating Factor Acetylhydrolase Susceptibility Of Sepsis

Objective:Sepsis was one of the leading causes of death in critically ill patients; pose serious challenges to the clinical treatment. In recent years, studies had shown that platelet activating factor acetylhydrolase (PAF acetylhydrolases, PAF-AH, also known as PLA2G7) to specific degradation of platelet activating factor which was an important pro-inflammatory cytokines. In septic disease PAF-AH had a potentially protective effect. PAF-AH gene single nucleotide polymorphisms could affect its enzyme activity, with a variety of inflammatory disease and its prognosis. However, currently the relation of sepsis and PAF-AH gene polymorphism was not clarified in domestic and abroad. In this study we used molecular biology methods to analysis PAF-AH gene Ala379Val and Val279Phe polymorphisms in patients with sepsis and explored the relations between polymorphisms and sepsis susceptibility and prognosis.Methods:1. Specimen collection:66 patients of sepsis group were selected from October 2008 to August 2009 in Tianjin two Third Grade Class hospitals admitted with sepsis. Based on diagnostic criteria of sepsis patients were divided into mild group and severe sepsis group; according to 28-day turn-over patients were divided into survival group and death group.68 cases of control group come from the healthy out-patient medical groups.2. By PCR-RFLP technique, PAF-AH gene exon 11 and 9 was amplified. Then PCR products were separately digested by restriction endonuclease Fnu4h I and Acl I. SNP variation and genotyping were directly determined by gel electrophoresis patterns. At the same time, PCR products containing allele gene polymorphism were sent to sequence analysis. PAF-AH gene Ala379Val and Val279Phe polymorphisms were analyzed in 66 cases of varying degrees of sepsis patients and 68 healthy controls. Then SNP genotype and allele frequency distribution were computed.Results:1. All the samples of the PAF-AH gene in the Val379Ala site had three kinds of genotypes:in 66 cases of sepsis group there were 1 homozygous Val/Val type, 19 heterozygous Val/Ala type,46 homozygous Ala/Ala type; in 68 cases of control group there were 2 Val/Val type,22 Val/Ala type,44 Ala/Ala type. The Val379Ala genotypic distribution and allele gene frequency in the patients with sepsis was not significantly different from those in the healthy controls; no statistically significant difference was observed among the survival group,the death group and the control group; no statistically significant difference was observed among the mild sepsis group, severe sepsis group and control group.2. PAF-AH gene of Val279Phe polymorphism could have three kinds of genotypes:All 66 patients in the sepsis group were the homozygous Val/Val type; control group 68 cases, only one case was homozygous Phe/Phe type, and the others were homozygous Val/Val type, not found heterozygous Val/Phe type. The Val279Phe genotypic distribution and allele gene frequency in the patients with sepsis was not significantly different from those in the healthy controls; no statistically significant difference was observed among the survival group,the death group and the control group; no statistically significant difference was observed among the mild sepsis group, severe sepsis group and control group.Conclusion:No associations were found between PAF-AH gene Val379Ala and Val279Phe polymorphisms and sepsis susceptibility, prognosis and severity.