Genetic background is different between sentinel and recurrent acute pancreatitis

Masamune, Atsushi; Ariga, Hiroyuki; Kaneda, Kiyoshi; Kakuta, Yoichi; Satoh, Kennichi; Satoh, Akihiko; Shimosegawa, Tooru

doi:10.1111/j.1440-1746.2011.06691.x

Cited by 25 publications

(14 citation statements)

References 25 publications

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“…However, the SPINK1 N34S variant increases the risk of alcoholic CP 5-fold, idiopathic CP 15-fold, and tropical CP 19-fold 45 . It is unlikely that SPINK1 mutations are a susceptibility factor for AP, but rather for RAP and CP 89, 90 . SPINK1 could be effective in controlling the effects of recurrent intra-pancreatic trypsin activation from a variety of etiologies, but mutations in SPINK1 might allow recurrent trypsin-associated injury to lead to development of fibrosis (Figure 4).…”

Section: Progression From Rap To Cpmentioning

confidence: 99%

Genetic Risk Factors for Pancreatic Disorders

2013

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A combination of genetic, environmental, and metabolic factors contribute to development and recurrence of acute and chronic pancreatitis; information on all of these is required to manage patients effectively. For example, variants that affect regulation of the protease, serine (PRSS)1-PRSS2 and claudin (CLDN)2 loci, rather than their coding sequences, interact with other genetic and environmental factors to affect disease development. New strategies are needed to use these data and determine their contribution to pathogenesis, because these variants differs from previously studied, rare variants in exons (coding regions) of genes such as PRSS1, SPINK1, cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsin (CTR)C, and calcium-sensing receptor (CASR). Learning how various genetic factors affect pancreatic cells and systems could lead to etiology-based therapies, rather than treatment of symptoms.

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Section: Progression From Rap To Cpmentioning

confidence: 99%

Genetic Risk Factors for Pancreatic Disorders

2013

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“…The p.N34S mutation has been found worldwide in CP patients and healthy controls, with an average allele frequency of 9.7% and 1%, respectively (Witt et al 2000;Pfützer et al 2000;Chen et al 2001;Bhatia et al 2002;Kume et al 2005;Aoun et al 2008). In addition to CP, we and others have reported that the p.N34S mutation is strongly associated with recurrent acute pancreatitis, but does not increase the risk of the first or sentinel acute pancreatitis event (Aoun et al 2010;Masamune et al 2011). The second most common mutation c.194+2T>C (IVS3+2T>C) has been reported in patients with idiopathic, familial, and alcoholic CP (Witt et al 2000;Pfützer et al 2000;Bhatia et al 2002;Kume et al 2005;Oh et al 2009;Ota et al 2010;Sun et al 2013).…”

Section: Spink1 Mutationsmentioning

confidence: 99%

Genetics of Pancreatitis: The 2014 Update

Masamune

2014

Tohoku J. Exp. Med.

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Chronic pancreatitis is a progressive inflammatory disease in which pancreatic secretory parenchyma is destroyed and replaced by fibrous tissue, eventually leading to malnutrition and diabetes. Alcohol is the leading cause in Western countries, but genetic factors are also implicated. Since the identification of mutations in the cationic trypsinogen (PRSS1) gene as a cause of hereditary pancreatitis in 1996, we have seen great progress in our understanding of the genetics of pancreatitis. It has been established that mutations in the genes related to the activation and inactivation of trypsin(ogen) such as PRSS1, serine protease inhibitor Kazal type 1 (SPINK1) and chymotrypsin C (CTRC) genes are associated with pancreatitis. In 2013, carboxypeptidase A1 (CPA1) was identified as a novel pancreatitis susceptibility gene. Endoplasmic reticulum stress in pancreatic acinar cells resulting from the mis-folding of mutated pancreatic enzymes has been shown to act as a novel mechanism underlying the susceptibility to pancreatitis. In Japan, the nationwide survey revealed 171 patients (96 males and 75 females) with hereditary pancreatitis in 59 families based on the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer criteria. Because about 30% of families with hereditary pancreatitis do not carry mutations in any of the known pancreatitis susceptibility genes, other yet unidentified genes might be involved. Next generation sequencers can perform billions of sequencing reactions with a read length of 150-250 nucleotides. Comprehensive analysis using next generation sequencers will be a promising strategy to identify novel pancreatitis-associated genes and further clarify the pathogenesis of pancreatitis.

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“…In support of the concept that persons with these genetic mutations have or will develop CP, Masumune et al (24) reported that mutations in the genes PRSS1 (R122H), SPINK1 (N34S) and PRSS3 (E32del) associated with recurrent but not single attacks of AP. The reader is referred to an update of the genetics of idiopathic CP and other pancreatic diseases in the present edition of Current Opinion.…”

Section: Genetics In Sentinel and Recurrent Acute Pancreatitis (Ap)mentioning

confidence: 99%

Chronic pancreatitis

DiMagno

2012

Current Opinion in Gastroenterology

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Purpose of review We review important new clinical observations in chronic pancreatitis (CP) reported in 2011. Recent findings Smoking increases the risk of non-gallstone acute pancreatitis (AP) and the progression of AP to CP. Binge drinking during Oktoberfest did not associate with increased hospital admissions for AP. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in CP is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90,000 USP U of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared to endoscopic treatment in patients advanced CP with a dilated main duct +/− pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with CP but ~30% of patients have significant side effects. Summary Patients with non-gallstone related AP or CP of any etiology should cease smoking. Results of this year’s investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in CP, and the mechanisms and treatment of neuropathic pain in CP.

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Genetic background is different between sentinel and recurrent acute pancreatitis

Abstract: The PRSS1 p.R122H mutation, SPINK1 p.N34S, and PRSS3 p.E32del variants were associated with recurrent, but not sentinel AP. The genetic background could possibly be different between sentinel and recurrent AP.

Cited by 25 publications

References 25 publications

Genetic Risk Factors for Pancreatic Disorders

Genetic Risk Factors for Pancreatic Disorders

Genetics of Pancreatitis: The 2014 Update

Chronic pancreatitis

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