[DOWNLOAD] "Association of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation/Variant/Haplotype and Tumor Necrosis Factor (TNF) Promoter Polymorphism in Hyperlipidemic Pancreatitis (Lipids, Lipoproteins, And Cardiovascular Risk Factors)" by Clinical Chemistry * Book PDF Kindle ePub Free
eBook details
- Title: Association of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation/Variant/Haplotype and Tumor Necrosis Factor (TNF) Promoter Polymorphism in Hyperlipidemic Pancreatitis (Lipids, Lipoproteins, And Cardiovascular Risk Factors)
- Author : Clinical Chemistry
- Release Date : January 01, 2008
- Genre: Chemistry,Books,Science & Nature,
- Pages : * pages
- Size : 259 KB
Description
Hypertriglyceridemia (HTG) [5] is associated with acute pancreatitis and is found in 3%-38% of patients with acute pancreatitis (1-5). HTG is the 3rd most frequent etiology of acute pancreatitis in Taiwan (6), accounting for about 10%-15% of patients with acute pancreatitis. In the absence of other etiologic factors and in the presence of high serum triglyceride (TG) concentrations (11.3 mmol/L), acute pancreatitis is considered to be secondary to HTG, (5, 7). Patients who present with significant HTG and pancreatitis usually have a preexisting abnormality in lipoprotein metabolism, such as lipoprotein lipase deficiency or apolipoprotein C deficiency (8). Mutations, such as in genes for lipoprotein lipase and apolipoprotein, have been reported to be associated with HTG, but their occurrence does not explain why some patients develop acute pancreatitis and others do not. Previous studies have been inconclusive regarding which HTG patients will develop pancreatitis (9-11) and in explaining why some HTG patients seldom develop pancreatitis. The mechanism by which HTG leads to pancreatitis is not clear. Unbound free fatty acids are toxic and may cause trypsinogen activation, which could then lead to injury of acinar cells or capillaries and thereby initiate acute pancreatitis (12, 13). Some HTG patients, however, seldom develop pancreatitis, even with marked increases in TG concentrations (2). Genetic factors may play important roles in susceptibility to pancreatic injury, as well as in the severity and evolution of the inflammatory process (8). In humans, the genes PRSS1 [6] [protease, serine, 1 (trypsin 1)], SPINK1 (serine peptidase inhibitor, Kazal type 1) (14), and CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] (15-17) and genes encoding factors that modulate the inflammatory response to pancreatic injury, such as TNF [tumor necrosis factor (TNF superfamily, member 2)] (18), are reportedly associated with acute recurrent pancreatitis (19) and chronic pancreatitis (20). In addition, mutations in these genes have enhanced the pancreatic inflammatory response in animal models. A transgenic mouse model expressing the Arg122His mutation in mouse trypsinogen displayed early-onset acinar injury, inflammatory cell infiltration, and enhanced response to cerulein-induced pancreatitis (21). Similarly, cftr(-/-) mice showed constitutive expression of proinflammatory cytokines and developed more severe pancreatitis episodes after cerulein stimulation (22). We evaluated the hypotheses that sensitization of ductal or acinar pancreas cells or cofactors is involved in the HTG process to induce acute pancreatitis and high serum TG concentrations and that mutations and functional variations of PRSS1, SPINK1, and CFTR, and TNF promoter polymorphisms are associated with hyperlipidemic pancreatitis (HLP).