ASSOCIATION OF TUMOR NECROSIS FACTOR - PROMOTER HAPLOTYPE WITH CHRONIC PANCREATITIS

Abstract

Background and Aims: The TNF-α promoter has been reported to play an important role in the pathogenesis of some inflammatory diseases. We hypothesized that TNF-α promoter might be among the susceptibility genes of nonfamilial chronic pancreatitis and conducted a genetic case-control study. In the present study, we used haplotype analyses of the TNF-α promoter with a permutation-based hypothesis testing method to determine the association between TNF-α promoter polymorphisms and chronic pancreatitis in a relatively homogeneous Taiwanese population. Methods: A total of 70 patients with documented nonfamilial chronic pancreatitis and 200 controls were selected. The controls were matched to cases on the basis with regard to age and gender. The TNF-α promoter polymorphism, including -1031(T/C), -863(C/A), -857(C/T), -308(G/A) and -238(G/A) were genotyped. Results: The -863A allele of the TNF-α promoter conferred increased risk for chronic pancreatitis (OR = 4.949; 95% CI 2.678-9.035). In multivariate analyses, the -863A and -1031C were independently associated higher susceptibility of chronic pancreatitis (P < 0.0001). In multilocus haplotype analysis, the TNF-α promoter haplotype profile was significantly different between cases and controls (x2 = 58.28461, P = 0.001). The TACAG, CACAG, TACGG TNF-α promoter increased susceptibility of chronic pancreatitis in Chinese. Conclusion: This study demonstrates the association of TNF-α promoter polymorphisms with nonfamilial chronic pancreatitis. TNF-α -863 promoter polymorphism and haplotype should be novel host factors to determine the susceptibility of Chinese to chronic pancreatitis. Further studies are needed to elucidate the mechanism in pancreatic fibrogenesis.