title: Tumor necrosis factor gene polymorphism results in high TNF level in sepsis and septic shock.
abstract: BACKGROUND
  Systemic sepsis releases several cytokines among which tumor necrosis factor alfa (TNFα) has emerged as key cytokine causing septic shock. Single Nucleotide Polymorphisms (SNPs) at positions -238, -308, -376 and +489 in the promoter region of TNF gene exhibit differential association to inflammation and increased TNF production in sepsis.
  
  
  METHODS
  This research work was carried out in 278 critically ill patients and 115 controls. The patients were divided into four groups: Healthy controls, SIRS, Sepsis and Septic shock. Plasma cytokine level was evaluated by ELISA. Specific sequences of TNF gene (-238, -308, -376, +489) were amplified using polychromase chain reaction (PCR). SNP detected by BamHiI, NcoI, FokI, TaiI restriction enzymes.
  
  
  RESULTS
  Mean plasma TNFα level in healthy Control group was 8.37 ± 2.23 pg/ml, in SIRS group, the mean plasma TNFα level was 77.99 ± 5.51 pg/ml, in Sepsis patients 187.1 ± 14.33 pg/ml and in septic shock 202.2 ± 14.85 pg/ml; range 56.17-417.1 pg/ml. SNP was studied among different patient groups, which showed a higher frequency of mutants among sepsis and shock patients as compared to control.
  
  
  CONCLUSIONS
  Plasma TNF alpha level was significantly high in patients with sepsis and septic shock. SNP of TNF gene showed significant association between polymorphism and development of severe sepsis and septic shock, this would help us in evaluating patients at high risk for septic shock and such patients needed to obtain a rational basis for therapy.
authors: Department of Anaesthesia, King Georges Medical University, Lucknow, U.P. 226 003, India. drnikhilkothari@gmail.com
authors: Nikhil
authors: N
authors: Kothari
authors: Jaishri
authors: J
authors: Bogra
authors: Haider
authors: H
authors: Abbas
authors: Monica
authors: M
authors: Kohli
authors: Anita
authors: A
authors: Malik
authors: Divya
authors: D
authors: Kothari
authors: Shivani
authors: S
authors: Srivastava
authors: Prithvi K
authors: PK
authors: Singh
mesh_terms: D000328:Adult; D003710:Demography; D004587:Electrophoresis, Agar Gel; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012772:Shock, Septic / Q000097:blood* / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*; D055986:Vital Signs
chemical_list: C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha