The Association Of A Single Nucleotide Polymorphism In Exon Of Transient Receptor Potential Melastatin 2 Gene With Sepsis

Background:Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection,which is a common complication after severe trauma,burn and major surgery.Sepsis is a major cause of death in critically ill patients.It has been shown that there were almost 20 million sepsis cases worldwide each year.The mortality of sepsis was still as high as 25%,although the progress of the implementation and promotion of the sepsis bundles including antibiotic therapy,fluid resuscitation and organ function support.It becomes a serious threaten to human health,which involving high cost of medical treatment and medical resources,and accounting for more than $20 billion(5.2%)of total US hospital costs in 2011.Sepsis is a complex syndrome and own to a dynamic process that originates from the host immune response to bacteria and varies according to the genetic predisposition,immune status and comorbid conditions of the host,the type of pathogen and the site and extent of infection.Studies from different populations in different regions have shown that the occurrence and development of sepsis have significant differences.Genetic variation,especially,single nucleotide polymorphisms,is one of the important factors affecting the susceptibility and the outcome of sepsis.Therefore,exploring and identifying potential markers and SNPs of susceptibility and outcome in sepsis will help to provide the theory basis of prevention and treatment.The pathophysiological mechanisms of sepsis is complex,immune cells recognize the pathogenic microorganisms through various receptors expressed on the cellular membrane,and participate in the occurrence and development of sepsis.Transient receptor potential melastatin 2(TRPM2),a nonselective Ca2+ permeable channel,is a membrane-receptor expressed abundantly on macrophages.Recent studies suggested that the transient receptor potential melastatin 2(TRPM2)channel played an important role in the regulation of immune and inflammatory response of monocytes/macrophages,which may involve in the pathogenesis of sepsis.The exon 11(Asp543Glu),is the only exonic SNP with high minor allele frequency of TRPM2.Deletion of a partial sequence of exon 11 containing SNP rs1556314,ablates the response of TRPM2 to H2O2 or ADP-ribose,and results in an irregulation of intracellular Ca2+ homeostasis and cellular oxidative stress response.It was also demonstrated that there was a significant association of TRPM2 genetic variants with BD in case-control and BD family.However,whether the single nucleotide polymorphisms(SNP)of TRPM2 have a association with sepsis is still unknow.Objective:To explore the association of TRPM2 SNP rs1556314 with the susceptibility and outcome of sepsis.Methods:After approval by the hospital and national ethics committee,in this case-control study,119 sepsis patients in ICU after diagnosis of sepsis in the First Affiliated Hospital of Zhejiang University were enrolled.The patients who were pregnant or whose age were less than 18 years were excluded.Furthermore,the patients with sepsis were divided into survivors(57)and non-survivors(62)on the basis of the outcome of 28 days in hospital.One hundred and twelve postoperative patienis without sepsis were enrolled as controls.After accquired informed consent of patients,five milliliter of peripheral whole blood was obtained form each individual through a veinous puncture(2%EDTA anticoagulation).Genomic DNA was isolated with QIAamp DNA Blood Mini Kit(Qiagen.Ltd.)from the peripheral whole blood.The genotypes of these individuals were tested using Polymerase Chain Reaction(PCR)Taqman allelic discrimination assays,the allelic frequencies were also tested.SPSS 19.0 software was used to analyzed the data.Quantitative data was presented as mean±SD,enumeration data expressed as a percentage.Differences in genotype and allele frequencies between sepsis patients and healthy controls were assessed by ?2 test.P value less than 0.05 was considered statistically significant.Results:There was no significantly difference in genotype frequencies and the allelic frequencies of TRPM2 SNP rs1556314 between septic patients and healthy control(P>0.05).Furthermore,when the patients with sepsis were divided into survivors and non-survivors,the genotype frequencies and allelic frequencies between the two sub-groups were also not significantly different(P>0.05).Conclusions:The TRPM2 SNP rs1556314 didn't have a significant association with the susceptibility and outcome of sepsis.