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Relevance of transforming growth factor-β1, interleukin-8, and tumor necrosis factor-α polymorphisms in patients with chronic pancreatitis


European Cytokine Network. Volume 18, Number 1, 1-7, March 2007, Research papers

Free Article  

Author(s) : Gy Farkas Jr., P Hofner, A Balog, T Takács, A Szabolcs, Gy Farkas, Yvette Mándi

Summary : Cytokine regulation may be an important factor in the susceptibility for the development of chronic pancreatitis\; transforming growth factor-β1 (TGF-β1) plays a central role in the pathogenesis of pancreatic fibrogenesis. The aim of our study was to analyse the relevance of TGF-β1, interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) polymorphisms in patients with chronic pancreatitis.Patients: of the 83 patients enrolled in the study, 43 were treated medically and 40 patients underwent surgical intervention. Healthy blood donors (n \= 75) served as controls.Methods: the polymorphisms of TGF-β1 +869 T→ C and IL-8 -251 T→A were determined by the ARMS method, while that of TNF-α -308 was investigated using NcoI RFLP.Results: there was a higher frequency (50%) of the TT genotype of TGF-β1 +869, with a concomitantly higher TGF-β1 level in the plasma (5.2 ± 1.7 ng/mL) of patients with chronic pancreatitis than in healthy blood donors (28% and 2.8 ± 0.9 ng/mL respectively). The number of TT homozygotes differed significantly between the patients who underwent surgical intervention and the controls, and even between the surgical and the non-surgical patients. The frequency of the T/A genotype with higher IL-8 production, was significantly higher in both groups of patients than in the controls (58% and 58% versus 40%). No correlation was found between the TNF-α -308 polymorphism and chronic pancreatitis.Conclusions: correlations of the TGF-β1 and IL-8 single nucleotide polymorphisms (SNPs) with chronic pancreatitis underline the importance of these cytokines in the pathomechanism of the disease. Moreover, it seems that the TT genotype of +869 TGF-β1 might be a risk factor for the development of a severe form of chronic pancreatitis, and could serve as a prognostic sign for any future surgical intervention or even repeat surgery. Further studies on a larger group of patients, in addition to a follow-up study, are necessary to confirm this preliminary observation.

Keywords : chronic pancreatitis, TGF-β, IL-8, TNF-α polymorphism

 

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