title: Clinical relevance of single nucleotide polymorphisms within the 13 cytokine genes in North Indian trauma hemorrhagic shock patients.
abstract: BACKGROUND
  The susceptibility to adverse outcome from critical injury (occurrence of sepsis, septic shock, organ dysfunction/failure, and mortality) varies dramatically due to different degrees of inflammatory response. We assessed the relationship of the genotype distribution of various cytokine gene polymorphisms (CGP) with regard to the development of sepsis, organ dysfunction or mortality in severely injured patients.
  
  
  METHODS
  Observational, hospital-based cohort study of 114 severely injured North Indian patients from New Delhi admitted to the Emergency Department (ED) of Trauma Centre, AIIMS. Patients were monitored from day first to discharge or death, measuring SOFA score, sepsis and septic shock occurrences up to one month. We have analyzed 13 cytokine genes, including the SNPs of structural and regulatory regions at 22 positions.
  
  
  RESULTS
  Sequence-specific primer based PCR indicated that eight polymorphic loci IL-1α /-889, IL-1β/-511, IL-1R (pstI 1970), TGF-β/ code 10, TNF-α/-308, TNF-α/-238, IL-6/+565 and IL-10/-1082, out of 22 SNPs are significantly associated with sepsis morbidity and outcome. Theses SNPs might be used as risk determinants of the outcome. Patients with IL-10 (-1082A/A) genotypes were found significantly higher in post traumatic sepsis patients and had a significantly higher risk to developed sepsis complication (p < 0.05, OR = 0.86, C.I = 0.08-8.8).In case of TNF-α (-308) position, GA and GG genotype patients have a significantly lower risk of poor outcome (p < 0.05, OR = 0.25, C.I = 0.01-1.3) and (p < 0.05, OR = 0.22, C.I = 0.01-0.5) in comparison to AA genotype. In this study, two polymorphisms (IL-1β (-511) and IL-1R) were significantly associated with the development of MOF and mortality, where as IL-1α (-889) polymorphism associated with susceptibility for sepsis. The distribution of haplotypes of TGF-β and IL-6 were also associated with sepsis susceptibility and outcome.
  
  
  CONCLUSIONS
  In conclusion, we have found that the alternations in the genotype and allele frequency of IL-1β (-511C/T), TNF-α (-308 G/A), TNF-α (-238 G/A) and IL-10 (-1082 G/A) genes are associated with an higher risk of sepsis development in trauma patients and outcomes.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. dablugupta10@gmail.com.
authors.forename: Dablu Lal
authors.initials: DL
authors.lastname: Gupta
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. pradeepbt13@gmail.com.
authors.forename: Predeep Kumar
authors.initials: PK
authors.lastname: Nagar
authors.affiliation: Department of Biostatics, All India Institute of Medical Sciences, New Delhi, India. vineetstats@gmail.com.
authors.forename: Vineet Kumar
authors.initials: VK
authors.lastname: Kamal
authors.affiliation: Department of Emergency Medicine, JPNATC, All India Institute of Medical Sciences, New Delhi, India. sanjeevbhoi@gmail.com.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Bhoi
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. dnrao311@rediffmail.com.
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics*; D018450:Disease Progression; D004636:Emergency Service, Hospital; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D017052:Hospital Mortality; D006801:Humans; D007194:India; D016015:Logistic Models; D008297:Male; D009102:Multiple Organ Failure / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D012771:Shock, Hemorrhagic / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology
chemical_list: D016207:Cytokines