Polymorphism of the TNF-alpha, HSP70-2, and CD14 genes increases susceptibility to severe acute pancreatitis.

OBJECTIVES

Proinflammatory cytokines and heat shock proteins play fundamental roles in the pathogenesis of acute pancreatitis. We studied whether polymorphisms of the tumor necrosis factor alpha (TNF-alpha), heat shock protein 70-2 (HSP70-2), and CD14 genes correlate with the severity of acute pancreatitis.

METHODS

Patients with acute pancreatitis (n = 77) of mixed etiology were grouped according to the severity of the disease on the basis of the Ranson scores. Healthy blood donors (n = 71) served as controls. TNF-alpha-308 polymorphism was determined by NcoI RFLP, HSP70-2 polymorphism by PstI RFLP, and CD14-159 polymorphism by melting point analysis.

RESULTS

There was a moderate increase in the frequency of the TNF1/2 genotype (P = 0.046) among patients with severe acute pancreatitis as compared with those with mild disease. A more significant increase was observed in the frequency of the HSP70-2 G allele between groups of patients with mild or severe pancreatitis (18.9% vs. 53%; P < 0.001). Conversely, the A/A genotype was markedly more frequent among the patients with mild pancreatitis (P < 0.0001). There was no significant correlation between CD14-159 promoter polymorphism and the severity of pancreatitis.

CONCLUSION

High frequencies of the HSP70-2 G and the TNF-alpha -308 A alleles were associated with risk of severe acute pancreatitis. Genotype assessments may be important prognostic tools to predict disease severity and the course of acute pancreatitis. Therefore, genotype assessments may also be used to guide treatment or to identify risk populations for severe acute pancreatitis.