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Context Alcohol is the major aetiological agent for both chronic pancreatitis and alcoholic liver disease. However, as only a minority of alcoholics develop either chronic pancreatitis or alcoholic liver disease, there are clearly genetic or environmental cofactors that determine individual susceptibility to these diseases. Objective To determine whether polymorphisms of the TNF gene may account for individual susceptibility to develop chronic pancreatitis or alcoholic liver disease. Design A controlled study. Patients We analyzed 73 patients with chronic pancreatitis, 103 healthy controls, 39 patients with alcoholic liver disease and 29 alcoholics without liver or pancreatic disease. Results The intermediate/low TNF secreting haplotype a6b5c1d3e3 was over-represented in chronic pancreatitis compared to healthy controls (OR=2.08; 95% CI: 1.07-4.06); P=0.019) and in alcoholic chronic pancreatitis compared to healthy controls (OR=2.08; 95% CI: 1.01-4.29; P=0.029). The high TNF secreting haplotypes, a2b3c1d1e3 and a2b5c2d4e3 were under-represented in chronic pancreatitis compared to healthy controls (OR=0.48; 95% CI: 0.22-1.04; P= 0.043) and in alcoholic chronic pancreatitis compared to alcoholic controls (OR=0.20; 95% CI: 0.05-0.77; P=0.014), respectively. Conclusion A reduced capacity to produce TNF may be responsible for the induction of chronic pancreatitis.