Cystic fibrosis gene mutations and pancreatitis risk: Relation to epithelial ion transport and trypsin inhibitor gene mutations

Noone, Peadar G.; Zhou, Zhaoqing; Silverman, Lawrence M.; Jowell, Paul S.; Knowles, Michael R.; Cohn, Jonathan

doi:10.1053/gast.2001.29673

Cited by 289 publications

(178 citation statements)

References 52 publications

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“…This frequency is higher than the 4.3% 20 and 5.0%, 31 similar to the 9.4%, 19 but much lower than the 18.8%, 7 23.1%, 28 25.9%, 16 and 28.6%, 18 reported in other studies. This discrepancy may be mainly due to the difference in the composition of patients chosen in these studies.…”

contrasting

confidence: 46%

“…In this regard, it is important to note that the same R122H mutation was also detected in one out of 39 well-characterised ICP patients in a just published study. 28 Moreover, this mutation was found in a patient diagnosed for 20 years as having alcoholic pancreatitis and with no family history of pancreatic disease. 29 Furthermore, a gene conversion event, a c.365*366GC4AT two base pair nucleotide change, which also results in a R122H mutation in PRSS1, was also detected in one Belgian with ICP.…”

Section: Discussionmentioning

confidence: 98%

“…Trans-heterozygous state with sequence variations in different genes exists in certain subjects To date, a combination of either a PRSS1 mutation plus a CFTR mutation, 28,40 a PRSS1 mutation plus a PSTI mutation, 41 or a CFTR mutation plus a PSTI mutation 28,31 has been occasionally reported. These rare cases strongly suggest an interaction between different susceptibility loci in the pathogenesis of the disease.…”

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confidence: 99%

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Determination of the relative contribution of three genes–the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene–to the etiology of idiopathic chronic pancreatitis

et al. 2002

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In the last 5 years, mutations in three genes, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the pancreatic secretory trypsin inhibitor (PSTI) gene, have been found to be associated with chronic pancreatitis (CP). In this study, using established mutation screening methods, we systematically analysed the entire coding sequences and all exon/intron junctions of the three genes in 39 patients with idiopathic CP (ICP), with a view to evaluating the relative contribution of each gene to the aetiology of the disease. Our results demonstrate that, firstly,`gain-of-function' mutations in the PRSS1 gene may occasionally be found in an obvious ICP subject. Secondly, presumably`loss-of-function' mutations in the PSTI gene appear to be frequent, with a detection rate of at least 10% in ICP and, finally, abnormal CFTR alleles are common: at least 20% of patients carried one of the most common CFTR mutations, and about 10% of patients were compound heterozygotes, having at least one`mild' allele. Thus, in total, about 30% of ICP patients carried at least one abnormal allele in one of the three genes, and this is the most conservative estimate. Moreover, a trans-heterozygous state with sequence variations in the PSTI/ CFTR genes was found in three patients. However, an association between the 5T allele in intron 8 of the CFTR gene and ICP remains unproven.

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contrasting

confidence: 46%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Determination of the relative contribution of three genes–the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene–to the etiology of idiopathic chronic pancreatitis

et al. 2002

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“…The latter is an idiopathic, juvenile, nonalcoholic form of CP widely prevalent in several tropical countries. By simultaneously analyzing 39 ICP subjects for common mutations of CFTR, SPINK1, and PRSS1, Noone et al 31 found that about 60% of their patients had at least one mutation in either CFTR or SPINK1, or both. Interestingly, the risk of pancreatitis was increased approximately fivefold by having one CFTR mutation, 20-fold by having SPINK1 N34S mutation, 40-fold by having two CFTR mutations (compound heterozygotes), and 900-fold by having N34S and two CFTR mutations.…”

Section: Discussionmentioning

confidence: 99%

Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the serine protease inhibitor, Kazal type 1 (SPINK1) gene in patients with alcoholic chronic pancreatitis

et al. 2003

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Susceptibility to alcoholic chronic pancreatitis (ACP) could be genetically determined. Mutations in cationic trypsinogen (PRSS1), cystic fibrosis transmembrane conductance regulator (CFTR), and serine protease inhibitor, Kazal type 1 (SPINK1) genes have been variably associated with both the hereditary and the idiopathic form of chronic pancreatitis (CP). Our aim was to analyze the three genes in ACP patients. Mutational screening was performed in 45 unrelated ACP patients and 34 patients with alcoholic liver disease (ALD). No mutation of PRSS1 was found in ACP and ALD patients. Three mutations of CFTR were detected in four ACP patients with a prevalence (8.9%) not significantly different from that observed (3.0%) in ALD patients and from that expected (3.2%) in our geographical area. Neither compound heterozygotes for CFTR nor trans-heterozygotes for CFTR/SPINK1 were found. One ACP patient (2.2%) was found to carry the most common mutation (N34S) of SPINK1 compared to none of the ALD patients (P ¼ NS). In five other patients (two with ACP and three with ALD) other rare variants, including P55S, were found. In contrast with the hereditary and the idiopathic forms of CP, in which mutations of PRSS1, CFTR, and SPINK1 genes may occur, ACP is still a 'gene(s)-orphan' disease. The supposed genetic susceptibility to ACP relies on other yet unknown gene(s) which could affect the alcohol metabolism or modulate the pancreatic inflammatory response to alcohol abuse.

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“…A study by Noone et al [53] revealed association of CFTR mutations with ICP and a possibility of its interaction with PRSS1 and SPINK1 mutations in western populations. However, the frequency of CFTR mutations was found to be lower in TCP patients [54] , and needs to be studied in a larger group of patients.…”

Section: Genetics Of Tcpmentioning

confidence: 99%

Genetic mechanisms underlying the pathogenesis of tropical calcific pancreatitis

Mahurkar¹,

Reddy²,

Rao³

et al. 2009

WJG

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Chronic pancreatitis is known to be a heterogeneous disease with varied etiologies. Tropical calcific pancreatitis ( TCP) is a severe form of chronic pancreatitis unique to developing countries. With growing evidence of genetic factors contributing to the pathogenesis of TCP, this review is aimed at compiling the available information in this field. We also propose a two hit model to explain the sequence of events in the pathogenesis of TCP.

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Cystic fibrosis gene mutations and pancreatitis risk: Relation to epithelial ion transport and trypsin inhibitor gene mutations

Abstract: CFTR-related pancreatitis risk correlates with having 2 CFTR mutations and reduced extrapancreatic CFTR function. The N34S PSTI mutation increased risk separately. Testing for pancreatitis-associated CFTR and PSTI genotypes may be useful in nonalcoholic pancreatitis.

Cited by 289 publications

References 52 publications

Determination of the relative contribution of three genes–the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene–to the etiology of idiopathic chronic pancreatitis

Determination of the relative contribution of three genes–the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene–to the etiology of idiopathic chronic pancreatitis

Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the serine protease inhibitor, Kazal type 1 (SPINK1) gene in patients with alcoholic chronic pancreatitis

Genetic mechanisms underlying the pathogenesis of tropical calcific pancreatitis

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