Association of tumour necrosis factor microsatellite haplotypes with chronic pancreatitis
AIMS: Recent evidence implicates the immune system in having a primary pathogenic role in the development of chronic pancreatitis (CP). This study examined the relationship between the tumour necrosis factor (TNF) gene and susceptibility to CP. METHODS: DNA was extracted from the blood of 40 patients with CP, 107 ethnically matched normal controls and 33 patients with alcohol-induced liver disease (alcoholic controls). Three microsatellite polymorphisms at the TNF locus were examined by the polymerase chain reaction, gel electrophoresis and autoradiography. RESULTS: The TNFa6 allele was significantly over-represented in patients with CP compared with normal controls (chi2 = 4.09, P = 0.043), and in those with alcoholic CP (n = 24) compared with alcoholic controls (chi2 = 4.63, P = 0.031). The three locus haplotypes 6-5-1 and 2-5-2 were significantly over-represented (chi2 = 4.14, P = 0.042) and under-represented (chi2 = 4.63, P = 0.042) respectively in patients with alcoholic CP compared with alcoholic controls. CONCLUSIONS: A TNF haplotype has been defined that is associated with CP. This is consistent with a genetically determined role for TNF in the immunopathogenesis of CP.
O'Reilly
DA
Departments of Surgery, Medicine and Molecular Medicine, Derriford Hospital, Plymouth, UK.
Sargen
KD
Dunlop
S
Demaine
AG
Kingsnorth
AN