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dc.contributor.authorSARGEN, KEVIN
dc.contributor.otherPeninsula College of Medicine and Dentistryen_US
dc.identifierNOT AVAILABLEen_US

Background and Aims Acute Pancreatitis is an inflammatory disorder of varied aetiology and outcome. Tumour necrosis factor (TNF) and interleukin-10 are important mediators of disease pathogenesis. To investigate if the TNF and IL-10 gene loci influence susceptibility to and severity of acute pancreatitis, 135 patients with acute pancreatitis, ethnically matched normal controls, and alcoholics without pancreatic disease were studied. Methods Aetiology was classified as being secondary to alcohol, gallstones, or idiopathic. Patients were stratified into groups according to disease severity by assigning an organ failure score. Three TNF microsatellite loci (TNFa, TNFb, and TNFc), the -308 polymorphism within the TNF gene, the IL-10.G microsatellite locus, and 3 hi-allelic polymorphisms in the 5' flanking region of the IL-l 0 gene were typed using the polymerase chain reaction. Results There was no difference in allelic frequency of any of the cytokine gene loci between groups stratified according to disease severity. When patients were stratified according to aetiology of disease there was a decrease in the frequency of the TNFa2 allele in those patients with alcoholic acute pancreatitis compared to controls (14.3 vs. 35.5%, χ²=7.24, p=0.007). There was also a reduction in the frequency of the IL-10.Gl3 allele in patients with alcoholic pancreatitis compared to controls (4.8 vs. 21.3%, χ² =6.46, p=0.011). Data is also presented showing that a number of haplotypes exist as well as linkage disequilibrium across all 4 loci of the IL-10 gene, which contrasts with findings from previous work. The 3 locus haplotypes GCC and ATA are in strongest linkage disequilibrium, as is the microsatellite allele G9 and -1117.A and G9 with the 3-locus haplotype ATA. Conclusions This work has identified an allele within the TNF gene locus, and an allele within the IL-1 0.G locus which have different frequencies in patients with alcohol induced acute pancreatitis compared to other aetiologies. This finding may in part explain individuals' differing susceptibility to the development of acute pancreatitis after excessive alcohol consumption. Haplotypes not previously described exist across the IL-10 locus.

dc.publisherUniversity of Plymouthen_US
plymouth.versionFull version: final and full version as approved by the examiners at the time of the award of your degreeen_US

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