INTRODUCTION: Tumor necrosis factor-alpha (TNF-alpha) has been implicated in acute severe pancreatitis (ASP). NcoI polymorphism exists in TNF gene promoter and influences TNF-alpha gene transcription. AIMTo determine the predictive value of plasma levels of TNF-alpha and its soluble receptors (sTNFR), TNF-alpha-308 and TNFB polymorphisms on the occurrence of ASP and ASP-associated early septic shock. METHODOLOGY: Genotypes were determined in patients (n = 208) and healthy controls (n = 116) by means of restriction fragment length polymorphism analysis of polymerase chain reaction products. Plasma concentrations of TNF-alpha and sTNFR were measured by ELISA. RESULTS: No significant differences were found in baseline concentrations of TNF-alpha and sTNFR between patients who had early septic shock and those who did not. Baseline TNF-alpha levels did not differ significantly in patients displaying different alleles of the TNF gene. The overall TNF2 allele frequency and TNFB2 allele frequency in patients with ASP were both comparable with those in controls. TNF2 frequency was significantly higher in patients with septic shock than in patients without early septic shock (53.8% versus 22.4%; p = 0.003), as was TNFB2 frequency (88.5% versus 63.2%; p = 0.015). CONCLUSION: The study found no association between ASP and the two polymorphisms examined, although some associations were found between TNF2 and TNFB2 alleles with the development of early septic shock in ASP. Plasma level of TNF-alpha or sTNFR was of little value in predicting the occurrence of early septic shock in ASP.
INTRODUCTION:Tumor necrosis factor-alpha (TNF-alpha) has been implicated in acute severe pancreatitis (ASP). NcoI polymorphism exists in TNF gene promoter and influences TNF-alpha gene transcription. AIMTo determine the predictive value of plasma levels of TNF-alpha and its soluble receptors (sTNFR), TNF-alpha-308 and TNFB polymorphisms on the occurrence of ASP and ASP-associated early septic shock. METHODOLOGY: Genotypes were determined in patients (n = 208) and healthy controls (n = 116) by means of restriction fragment length polymorphism analysis of polymerase chain reaction products. Plasma concentrations of TNF-alpha and sTNFR were measured by ELISA. RESULTS: No significant differences were found in baseline concentrations of TNF-alpha and sTNFR between patients who had early septic shock and those who did not. Baseline TNF-alpha levels did not differ significantly in patients displaying different alleles of the TNF gene. The overall TNF2 allele frequency and TNFB2 allele frequency in patients with ASP were both comparable with those in controls. TNF2 frequency was significantly higher in patients with septic shock than in patients without early septic shock (53.8% versus 22.4%; p = 0.003), as was TNFB2 frequency (88.5% versus 63.2%; p = 0.015). CONCLUSION: The study found no association between ASP and the two polymorphisms examined, although some associations were found between TNF2 and TNFB2 alleles with the development of early septic shock in ASP. Plasma level of TNF-alpha or sTNFR was of little value in predicting the occurrence of early septic shock in ASP.
Authors: B D Freeman; C R Kennedy; H L Frankel; B Clarridge; D Bolcic-Jankovic; E Iverson; E Shehane; A Celious; B A Zehnbauer; T G Buchman Journal: Pharmacogenomics J Date: 2009-12-08 Impact factor: 3.550