TNF -308G > a promoter polymorphism (rs1800629) and outcome from critical illness

Abstract

Background:The susceptibility to adverse outcome from critical illness (occurrence of sepsis, septic shock, organ dysfunction/failure, and mortality) varies dramatically due to different degrees of inflammatory response. An over expression of tumor necrosis factor alpha (TNF-α) can lead to the progression of the inflammatory condition. Objective: We assessed the relationship of the genotype distribution of -308G >A TNF-α polymorphism with regard to the development of sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients. Methods: Observational, hospital-based cohort study of 520 critically ill Caucasian patients from southern Brazil admitted to the general ICU of São Lucas Hospital, Porto Alegre, Brazil. Patients were monitored daily from the ICU admission day to hospital discharge or death, measuring SOFA score, sepsis, and septic shock occurrences. The -308G >A TNF-α SNP effect was analyzed in the entire patient group, in patients with sepsis (349/520), and in those who developed septic shock (248/520). Results: The genotypic and allelic frequencies were -308GG = 0.72; -308GA = 0.27; -308AA = 0.01; -308G = 0.85; -308A = 0.15. No associations were found with sepsis, septic shock, organ dysfunction, and/or mortality rates among the TNF-α genotypes. Our results reveal that the -308G >A TNF-α SNP alone was not predictive of severe outcomes in critically ill patients. Conclusion: The principal novel input of this study was the larger sample size in an investigation with -308G > A TNF-α SNP. The presence of -308A allele is not associated with sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients.

Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) single nucleotide polymorphisms: Importance in ARDS in septic pediatric critically ill patients

“…A recent study evaluating 1136 adult Caucasian septic patients did not report any association between SNP TNF-308 and sepsis mortality [17]. Similar results were reported from two Brazilian studies with adult patients [18,19]. In contrast, a Japanese study with 123 septic adult patients [46] as well a Serbian study of 106 critically ill patients [47] reported increased risk for sepsis mortality associated with TNF-308GA.…”

“…However, two recent studies in Brazilian adult patients with sepsis did not confirm an association of TNF or LTA SNPs with clinical outcomes [18,19]. In addition to ethnicity, age may be a major cause of discrepancies among studies on the prevalence and clinical presentation of infectious diseases.…”

Tumor necrosis factor-α −308G/A and −238G/A polymorphisms are associated with increased risks of sepsis: evidence from an updated meta-analysis

“…All the 26 studies investigated the association between TNF‐α −308G/A polymorphism and risk of sepsis. Among them, 12 studies were conducted in Asian populations , 10 in Caucasian populations , and four in mixed populations (more than two ethnic groups) . A majority of studies (80.8%) were performed in adult populations, only four studies in pediatric populations .…”

The role of Tumor necrosis factor alpha −308 G>A promoter polymorphism in pediatric community acquired pneumonia

“…In addition, analysis of TNF-α −308 G>A promoter polymorphism was performed to all patients and controls by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) as previously described [17]:-…”