Relevance of transforming growth factor-beta1, interleukin-8, and tumor necrosis factor-alpha polymorphisms in patients with chronic pancreatitis.
Cytokine regulation may be an important factor in the susceptibility for the development of chronic pancreatitis; transforming growth factor-beta1 (TGF-beta1) plays a central role in the pathogenesis of pancreatic fibrogenesis. The aim of our study was to analyse the relevance of TGF-beta1, interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) polymorphisms in patients with chronic pancreatitis.


METHODS
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-beta1 +869 T--> C and IL-8 -251 T-->A were determined by the ARMS method, while that of TNF-alpha -308 was investigated using NcoI RFLP.


RESULTS
there was a higher frequency (50%) of the TT genotype of TGF-beta1 +869, with a concomitantly higher TGF-beta1 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-alpha -308 polymorphism and chronic pancreatitis.


CONCLUSIONS
correlations of the TGF-beta1 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-beta1 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.
Farkas
Gyula
G
Department of Surgery, University of Szeged, Hungary.
Hofner
Peter
P
Balog
Attila
A
Takács
Tamas
T
Szabolcs
Annamaria
A
Farkas
Gyula
G
Mándi
Yvette
Y
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D050500:Pancreatitis, Chronic / Q000097:blood / Q000235:genetics* / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D016209:Interleukin-8; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha