Tumour necrosis factor microsatellite haplotypes are associated with chronic pancreatitis

JOP. 2006 Jan 11;7(1):14-26.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcoholism / complications
  • Alcoholism / genetics
  • Base Sequence
  • DNA / genetics
  • Female
  • Gene Expression Regulation
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Haplotypes*
  • Humans
  • Liver Diseases, Alcoholic / etiology
  • Liver Diseases, Alcoholic / genetics
  • Male
  • Microsatellite Repeats / genetics*
  • Middle Aged
  • Molecular Sequence Data
  • Pancreatitis, Chronic / etiology
  • Pancreatitis, Chronic / genetics*
  • Polymorphism, Genetic
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Tumor Necrosis Factor-alpha
  • DNA