Polymorphic genes of HSP-70–2, TNF-alpha, and CD14 in patients with acute pancreatitis

Aims: We hypothesized that the polymorphism of the TNF gene locus and of HSP70 may influence disease susceptibility and course in acute pancreatitis (AP). Moreover, the role of genetic polymorphism of the LPS receptor CD14 could not be excluded.

Methods: DNA from 77 patients with AP was used for genetic experiments. The patients were grouped according to Ranson gene was determined by NcoI RFLP. The -308 polymorphism of TNF- polymorphism for HSP70–2 gene by PstI RFLP, and the CD14–159 polymorphism by melting point analysis. DNA was isolated from healthy controls (n=71).

Results: No significant difference was noted in the frequency of the TNF 2 allele, or between the groups stratified according to RS. The frequency of CD14–159 TT genotype only moderately was higher in patients with severe AP (p=0.045). There was significant difference in the frequency of HSP70–2 G allele between the groups of patients with severe AP (RS: 6.2) and the normal controls (53% vs. 35%, p=0.002), and especially between groups of patients with mild (RS: 2.8) and severe AP (18% vs. 53%; p<0001). Alternatively, the “protective&rdquor; AA genotype is markedly more frequent among the patients who have only a mild form of AP.

Conclusion: The high frequency of HSP70–2 G allele -with a concomitant lower HSP70 production -in severe AP provides further evidence that genetic determination of the defense mechanisms in AP is rather dependent on the polymorphism of the HSP genes than on that of the TNF-alpha or CD14 genes. The allele A of the HSG70–2 gene may be associated with less progressive disease in AP, thereby suggesting a clinical value of the genotype assessment of the gene.