Tumor Necrosis Factor-alpha Gene Single-nucleotide Polymorphisms Are Associated With Severe Adult Community Acquired Pneumonia In Chinese

Objectives:Pneumonia is a disease characterized by inflammatory reaction in matrix and parenchyma of lung.It has been identified that pneumonia is the result of an environmental insult and the response of the host that is primarily genetically predetermined.Recent studies indicate that coding polymorphisms in Tumor necrosis factor-α(TNF-α) are significantly associated with susceptibility and severity to pneumonia.TNF-αparticipate in the establishment of inflammatory lesions in pneumonia.High production of TNF-αmay relates to the severity of pneumonia.There have already been several studies examining the association between pneumonia and single nucleotide polymorphisms(SNPs) that affect the productivity of TNF-α.SNPs of TNF-α,-1031,-863,-857,-308 and -238 have been identified.There have already been several studies examining the association between inflammatory and SNPs that affect cytokine productivity and prognosis of sepsis,however,the results of these studies were in variation.For further research on gene mutation in pneumonia patients,we investigated whether polymorphisms in SNPs have any relations on individual susceptibility to the development of pneumonia.Methods:67 Chinese patients with pneumonia,50 healthy controls were enrolled.Peripheral blood was collected from patients and genomic DNA extraction was performed,then 5 pairs of primers were designed to amplify the sequences containing TNF-α-1031T/C,-863C/A,-857C/T, -308G/A and -238G/A.Then restriction fragment length polymorphism(RFLP) were performed to detect SNPs of TNF-αgene.The concentration of TNF-αin plasma was detected by ELISA.We also selected the clinical and laboratorial items for the research.The data of age and concentration of TNF-αin blood were analyzed by t test,the data of frequency of allele and prognosis such as morbility and mortality of severe adult community acquired pneumonia were analyzed by Chi square.Result:1,The frequencies of polymorphic genetpyes of foregoing SNPs were similar to the those published.The TNF-α-238A is rare in Chinese.The frequency of subjects who carried at least one variant allele in TNF-α-1031,-863,-857,-308,-238 SNPs among pneumonia patients was significantly higher than in healthy subjects.And who carried variant allele in TNF-α-308A allele among adult severe community acquired pneumonia patients was significantly higher than in common pneumonia patients,and their prognosis was unfavourable usually.2,The concentration of TNF-αin pneumonia patients was higher than those in controls,but there was no significant between common pneumonia patients and SCAP patients.Conclusion:The concentration of TNF-αin plasma elevate in inflammation.TNF-α-308A allele appears to be associated with susceptibility and severity to pneumonia in Chinese populations,and who carry TNF-α-308A is to trend to unfavourable prognosis.