Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiopathic chronic pancreatitis (ICP) is the leading cause of nonalcoholic chronic pancreatitis. This study examined a series of patients with ICP to determine the prevalence and role of mutations of the cystic fibrosis gene (CFTR) and of a trypsin inhibitor gene (PSTI). Genetic testing was done in 39 patients with ICP. In this series, 17 patients had CFTR mutations and 9 had PSTI mutations. Pancreatitis risk was increased 14-fold by having the N34S PST1 mutation, 40-fold by having two abnormal copies of CFTR, and 600-fold by having both. In patients with two CFTR mutations, extrapancreatic clinical findings and nasal bioelectric responses suggested reduced residual CFTR protein function. Thus, pancreatitis risk showed complex inheritance and was highest in individuals who have abnormalities in both the pancreatic ducts (CFTR) and acini (PSTI). These findings indicate that PSTI is a modifier gene for CFTR-related ICP and have implications for the classification, diagnosis, and pathogenesis of pancreatitis.
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PMID:Idiopathic pancreatitis related to CFTR: complex inheritance and identification of a modifier gene. 1222 54

Cystic fibrosis is rare in the Asian population, and is often associated with consanguinity and rare genotypes. We report on a 23-year-old Asian man from a consanguineous pedigree referred to the regional cystic fibrosis unit after a diagnosis of congenital bilateral absence of the vas deferens during investigations for infertility. A detailed history revealed several previous episodes of acute pancreatitis. Full diagnostic appraisal showed homozygosity for a novel cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation, but normal sweat test and nasal potential difference studies. An endoscopic retrograde cholangiopancreatogram (ERCP) showed chronic pancreatitis with bulky side branches. The vas deferens and the pancreas appeared exquisitely sensitive to mild CFTR dysfunction. Patients with cystic fibrosis and unexplained upper abdominal pain should be screened for pancreatitis, and consideration should be given to screening patients with idiopathic pancreatitis for mutations in the CFTR gene.
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PMID:Cystic fibrosis presenting as acute pancreatitis and obstructive azoospermia in a young adult male with a novel mutation in the CFTR gene. 1242 49

Alcoholic chronic pancreatitis and obstructive chronic pancreatitis are the most frequent and the better characterized types of pancreatitis. Recent advances in biology and genetics have brought new insights into the understanding of rare forms of chronic pancreatitis such as tropical chronic pancreatitis, hereditary chronic pancreatitis and chronic pancreatitis in cystic fibrosis. Some other rare forms of chronic pancreatitis have been identified: eosinophilic chronic pancreatitis, chronic pancreatitis after radiotherapy or during hypercalcemia, minimal change chronic pancreatitis and chronic pancreatitis associated with gut diseases or connectivitis. Recently, a particular form of non alcoholic chronic pancreatitis with duct destruction has been described often presenting as a pancreatic mass, leading in some cases to surgical resection of the pancreas. New insights into the understanding of chronic pancreatitis lead to new physiopathological concepts, and many arguments suggest that combined factors may lead to chronic inflammatory lesions of the pancreas.
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PMID:[Uncommon types of chronic pancreatitis]. 1248 56

The development of new drug formulations of pancreatine based on the principle of microdosage with a pH-sensitive coating produced the most demonstrative clinical result--a considerable increase in duration and quality of life of patients with chronic pancreatitis and cystofibrosis, most of which are children. Clinical studies confirmed high efficiency and safety of Panzytrat in open and double blind comparative clinical studies with the participation of 4,557 patients with chronic pancreatitis, mucoviscidosis, and pancreathogenous digestion disorders. In addition to the above-mentioned symptoms, indications for application of Panzytrat also include any clinical symptoms of the pancreas relative excretory insufficiency, in particular, states after oncological diseases and surgical operations (obstruction of ducts, resection, cholecystectomy, etc.) up to a failure to adhere to a diet and overeating.
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PMID:[Use of Panzytrat in the replacement therapy of exocrine pancreatic insufficiency (an analytical review)]. 1250 76

Mutations of three major genes are associated with an increased risk of acute and chronic pancreatitis: the cationic trypsinogen (PRSS1) gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and the pancreatic secretory trypsin inhibitor (PSTI) or serine protease inhibitor, Kazal type 1 (SPINK1) gene. Some autosomal dominant forms of hereditary pancreatitis are associated with mutations of the PRSS1 gene, which can be readily identified by genetic testing. Mutations of the CFTR gene can lead either to cystic fibrosis or to idiopathic chronic pancreatitis, and to a variety of cystic fibrosis-associated disorders, including congenital bilateral absence of the vas deferens and sinusitis. These mutations, as with those of the SPINK1 (or PSTI) gene, are prevalent in North America; thus, the presence of such a mutation in an asymptomatic person does not confer a high risk of developing pancreatitis. Combinations of mutations of the PRSS1 and SPINK1 genes lead to more severe disease, as indicated by an earlier onset of symptoms, which suggests that SPINK1 is a disease modifier. The major fear expressed by potential candidates for genetic testing is that the results could lead to insurance discrimination. Studies of the positive predictive value of genetic tests are hampered by recruitment bias and lack of knowledge of family history of pancreatitis. Genetic testing is most useful for persons for whom family members have already been found to exhibit a particular pancreatitis-associated mutation. In the future, increased knowledge of the myriad genetic causes of pancreatitis, as well as advances in the diagnosis and treatment of early chronic pancreatitis, should enhance the utility of genetic testing.
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PMID:Motion--genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: arguments for the motion. 1256 Aug 56

Mutations of two genes, the cystic fibrosis transmembrane conductance regulator gene (CFTR) and the pancreatic secretory trypsin inhibitor gene (PSTI), are associated with an increase in the risk of idiopathic chronic pancreatitis. Persons who have mutations of both CFTR alleles (one severely and one mildly affected) are especially susceptible to this disease. Because these compound heterozygotes have sufficient residual CFTR function, they do not develop cystic fibrosis lung disease. One PSTI mutation, N34S, independently increases the risk of pancreatitis. Thus, the risk of pancreatitis is greatest among individuals who are CFTR compound heterozygotes and who also have the PSTI mutation. Nonetheless, most people with CFTR and PSTI mutations do not develop pancreatitis. This fact indicates that environmental influences and gene-gene interactions also affect pancreatitis risk. Although CFTR and PSTI genetic testing can identify persons at an increased risk of pancreatitis, there are several reasons why the routine screening of individuals with nonhereditary pancreatitis is not recommended at this time: most disease-associated mutations are not detected by readily available techniques, genetic counselling guidelines do not exist, most patients with mutations do not develop pancreatitis and the results of testing do not affect the clinical management of pancreatitis.
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PMID:Motion--genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: arguments against the motion. 1256 Aug 55

Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited dominant, recessive, or complex as a result of mutations in the above mentioned or yet unidentified genes. Evaluation of patients with CP should include genetic testing. Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterised by pancreatic insufficiency and chronic bronchopulmonary infection. The progression and severity of pulmonary disease differs considerably between people with identical CFTR mutations and does not seem to correlate with the type or class of the CFTR mutation. The identification of further disease modifying genetic factors will increase the pathophysiological understanding and may help to identify new therapeutic targets.
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PMID:Chronic pancreatitis and cystic fibrosis. 1265 80

Aberrant membrane transport caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is associated with a wide spectrum of respiratory and digestive diseases as well as cystic fibrosis. Using a gene scanning method, we found 11 polymorphisms and mutations of the CFTR gene in the Korean population. Individual variants at these sites were analyzed by conventional DNA screening in 117 control and 75 patients having bronchiectasis or chronic pancreatitis. In a haplotype determination based on a Bayesian algorithm, 15 haplotypes were assembled in the 192 individuals tested. Several haplotypes, especially with Q1352H, IVS8 T5, and E217G, were found to have disease associations in a case-control study. Notably, a common polymorphism of M470V appears to affect the intensity of the disease association. Among the two haplotypes having IVS8 T5, the T5-V470 haplotype showed higher disease association than the T5-M470 haplotype. In addition, a Q1352H mutation found in a V470 background showed the strongest disease association. The physiological significances of the identified mutations were rigorously analyzed. Non-synonymous E217G and Q1352H mutations in the M470 background caused a 60-80% reduction in CFTR-dependent Cl(-) currents and HCO3(-) -transport activities. Surprisingly, the additional M470V polymorphic variant with the Q1352H mutation completely abolished CFTR-dependent anion transport activities. These findings provide the first evidence on the importance of CFTR mutations in the Asian population. Importantly, the results also reveal that interactions between multiple genetic variants in cis affect the final function of the gene products.
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PMID:A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases. 1295 61

We report the case of a patient suffering from idiopathic chronic pancreatitis (ICP) and compound heterozygous for mutations G542X and S1235R of the cystic fibrosis transmembrane regulator (CFTR) gene. The patient had normal sweat test and no other clinical sign usually linked with a typical or moderate pathology (bronchiectasis, nasal polyposis, congenital absence of the vas deferens) of the CFTR gene. G542X is a severe mutation, which is usually found in classical cystic fibrosis when associated with other severe mutations. S1235R is a quite rare abnormality recently reported as being potentially pathogenic when combined in trans with a second CF mutation. Our case is quite similar to the only other six patients in the literature in whom only the pancreas is affected and who bear a rare mutation with moderate effect. The history and the clinical features of our patient indicate an unambiguous isolated ICP in which the presence of the S1235R mutation--in trans with regard to G542X--is likely responsible for the ICP phenotype. This case could throw light on some of the as yet poorly known abnormalities of the CFTR gene in the ICP phenotype.
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PMID:Isolated idiopathic chronic pancreatitis associated with a compound heterozygosity for two mutations of the CFTR gene. 1458 56

Chronic pancreatitis is most frequently associated with alcohol abuse. This should however not always automatically be accepted as the presumed cause. When the history is doubtful, uncommon etiologies must be considered as is illustrated by the present case. A 38 years old man was in the past 20 years treated for chronic pancreatitis ascribed to ethylisme although he always denied this. When the diagnosis was eventually questioned, new investigations showed slightly elevated sweat electrolyte concentrations and a delta F508/R117H genotype compatible with cystic fibrosis (CF). Demonstration of mild respiratory abnormalities, obstructive azoospermia and CF in his brother supported this diagnosis. Although rarely, pancreatitis typically develops in the kind of CF patients with milder genotypes and less severe symptoms. Systematic analysis for genetic mutations in patients with idiopathic chronic pancreatitis (ICP) revealed however that this mild form of CF is a less exceptional cause than thought. As CF patients increasingly survive into adulthood this disease should be considered as a possible etiology in the differential diagnosis of pancreatitis at all ages.
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PMID:Cystic fibrosis: an unusual cause of chronic pancreatitis. 1461 62


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