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Title: Individual susceptibility to acute & chronic pancreatitis
Author: O'Reilly, Derek A.
ISNI:       0000 0001 3454 1268
Awarding Body: Universities of Exeter and Plymouth
Current Institution: University of Exeter
Date of Award: 2007
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Aims: To elucidate individual susceptibility to acute and chronic pancreatitis by examining candidate genes: tumour necrosis factor (TNF), cationic trypsinogen (PRSS1) and serine protease inhibitor, Kazal type 1 (SPINK1) in patients with acute and chronic pancreatitis. To examine the role of the transcription factors, nuclear factor-?B (NF-?B) and heat shock factor-1 (HSF-1) in acute pancreatitis. Results: The TNF a6b5c1d3e3 haplotype is positively associated with chronic pancreatitis (OR= 2.08 (95% CI: 1.12-3.88; X2=5.49, P=0.019); the TNF a2b3c1d1e3 and a2b5c2d4e3 haplotypes are negatively associated (OR= 0.48 (95% CI: 0.23-0.99; X2=4.08, P=0.043 and OR= 0.20 (95% CI: 0.05-0.77; Fisher's P=0.014, respectively). The PRSS1 R122H mutation was detected in 1 out of 36 patients with alcoholic pancreatitis and 3 members of a hereditary pancreatitis family. The N291, A16Vand -28deITCC mutations were not detected in patients or controls. The SPINK1 N34S mutation is associated with acute pancreatitis in UK and German populations (OR= 3.312 (95% CI: 1.805-6.078), P<0.001, X2 test). The mean age of those AP patients with the N34S variant was 11.9 years younger than those AP patients without N34S in the UK population. A novel variation (c.274C>T) in the 3' untranslated region was found in an acute pancreatitis patient. N34S is also associated with alcoholic chronic pancreatitis in UK, German and Swiss populations (P<0.001). Systemic NF-?B activation occurs in acute pancreatitis compared to healthy controls (P=0.004). Systematic activation of HSF-1 was observed in acute pancreatitis compared to healthy controls (P=0.053). However, activation was significantly greater in those who had mild pancreatitis compared to those who had severe acute pancreatitis (P=0.036). HSF-1 was inversely correlated with acute physiology score (r=-0.49; P=0.019) and APACHE II score (r=-0.47; P=0.026).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available