Study On The Correlation Between TNF-α Gene Polymorphism And Sepsis

Sepsis is a common complication after the severe injury such as burn, shock, infection and major surgery operation.Sepsis is a syndrome caused by the infection of systemic inflammation response syndrome, If early stage of sepsis cannot be cured, it can develop to sepsis shock and multiple organ dysfunction syndrome, even to multiple organ failure(MOF).MOF is a major cause of high mortality of critical patients.Sepsis is a syndrome which threat the healthy of human greatly.Sepsis is understood gradually in the long period clinical practice.A great effort has been done to enhance the therapeutic effect and decrease the morbidity and the mortality of sepsis.The mechanism of sepsis is complicated, both environmental and genetic factors contribute to the pathogenesis of sepsis. During this proeess the inflammatory factor play the critical roles and the ascent and decrease of inflammatory factor will influence the outcome of sepsis.Among the major inflammatory TNF-a play the important roles in process of sepsis. For the accumulation of cases in our region and the establishment of individual treatment, we studied the sepsis through the gene and the expression of the protein, and provided a research platform for further study.Objectivs:1.The aim of this study is to investigate the concentration of TNF-a in plasma in sepsis patients> SIRS patients and controls; 2.Genotype was performed to explore the initial mechanism of sepsis., to evaluate the sensitive individuals scientificly and to provide individual treatment.Single nucleotide polymorphism of TNF-a-238G/A and-308G/A in promoter of TNF-a were investigated to understand the regularity of sepsis from gene polymorphism aspects.Methods:1. Select 32 patients with severe sepsis and 48 patients with SIRS as the patient group who were admitted to ICU in the second hospital of Tianjin medical university and the kindergarden persons as controls between October,2009 and September,2010. Collect their blood samples to measure; 2. TNF-a level in plasma measured by ELISA.; 3. USE the method of PCR and RFLP to investigate the gene type on site 308 and 238 of TNF-a among severe sepsis patients group,SIRS patient group and controls.Results:We have measured the TNF-a level of 80 patients and 50 kindergarden persons by ELISA as followings: the TNF-a level of patients(77.418±10.019pg/ml) was higher than the kindergarden persons'(15.955±3.728pg/ml) (P＜0.05) which had statistically significant; At the same time, the TNF-a level of sepsis patients(84.255±8.106pg/ml) was higher than the SIRS patients (72.859±8.506 pg/ml) (P＜0.05) which also had statistically significant.In the study of gene polymorphism, on Site TNF-a-238,the frequece of AA,GA, GG was 3.125%,18.750%,78.125% in sepsis patients, and 0.000%,14.583%, 85.417% in the SIRS patients, and 0.000%,12.000%,88.000% in the kindergarden persons。By means ofΧ2 examination, there was no statistically significant on the gene type of three groups (Χ2=3.901, P=0.42>0.05), and there was no statistically significant on the frequence of Gene A, G of three groups. (Χ2=2.347, P=0.309>0.05);on Site TNF-a-308,the frequece of AA, GA, GG was 6.250%,18.750%,75.000% in sepsis patients, and 2.084%,14.583%,83.333% in the SIRS patients, and 0.000%,14.000%,86.000% in the kindergarden persons。By means ofΧ2 examination, there was no statistically significant on the gene type of three groups (Χ2=3.934, P=0.415>0.05), and there was no statistically significant on the frequence of Gene A, G of three groups. (Χ2=3.292, P=0.193>0.05).Above all, the persons of there groups had gene polymorphism on Site TNF-a-238 and TNF-a-308,and their gene types and frequence of Gene A, G had no difference.Conclusions:l.A significant difference between infectious patients and controls on the level of TNF-a was found in this study;The level of TNF-a in plasma was associated with infection level to some extent; 2.The study of gene polymorphism on site 238 and site 308 of TNF-a showed that there were two alleles G and A,and three SNPs GG, GA, AA. There was no significant association between gene polymorphism and infection level.