scholarly journals Motion-Genetic Testing is Useful in the Diagnosis of Nonhereditary Pancreatic Conditions: Arguments for the Motion

2003 ◽  
Vol 17 (1) ◽  
pp. 47-52 ◽  
Author(s):  
David C Whitcomb
Keyword(s):  
Cystic Fibrosis ◽  
Chronic Pancreatitis ◽  
Genetic Testing ◽  
Severe Disease ◽  
Bilateral Absence ◽  
Recruitment Bias ◽  
Increased Risk ◽  
Cationic Trypsinogen ◽  
Disease Modifier ◽  
Acute And Chronic Pancreatitis

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 thePRSS1gene, which can be readily identified by genetic testing. Mutations of theCFTRgene 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 theSPINK1(orPSTI) 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 thePRSS1andSPINK1genes lead to more severe disease, as indicated by an earlier onset of symptoms, which suggests thatSPINK1is 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.

Possibilities of the early diagnosis and prognosis of complicated clinical forms of chronic pancreatitis

2021 ◽  
Vol 29 (2) ◽  
pp. 267-276
Author(s):  
Sergey V. Tarasenko ◽  
Alexander A. Natalskiy ◽  
Oleg D. Peskov ◽  
Aleksey Yu. Bogomolov ◽  
Aleksandr A. Nikiforov ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Chronic Pancreatitis ◽  
Structural Changes ◽  
Severe Disease ◽  
Control Group ◽  
Lower Efficiency ◽  
University Center ◽  
Clinical Forms ◽  
Cystic Form ◽  
Cationic Trypsinogen

AIM: This study aimed to improve the methods for the diagnosis of complicated clinical forms of chronic pancreatitis (CP) by evaluating the clinical significance of the polymorphisms of the genes of cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (SPINK1), transmembrane regulator of cystic fibrosis (CFTR), and alcohol dehydrogenase (ADH) in patients with complicated and uncomplicated forms of CP. MATERIALS AND METHODS: The study was carried out on the clinical base of the Department of Hospital Surgery, Ryazan State Medical University, Center for Surgery of Liver, Pancreas, and Biliary Tract in Ryazan in 20142019. A total of 108 patients of both genders aged 2565 years were examined. Of these patients, 38 were surgically treated for complicated CP, 20 had complicated CP without surgery, and 50 had uncomplicated CP (control group). A comparative clinical study with the control group of patients was performed, and the genotype was simultaneously determined on days 1 and 10 under controlled laboratory parameters. DNA was isolated from the leukocytes of the whole blood by using a DNA-expressing blood reagent (OOO NPF Litekh, Russia) for further analysis. RESULTS: No polymorphism of cationic trypsinogen PRSS1 gene and cystic fibrosis-2 CFTR2 gene was found. The predictive value of these polymorphisms was insignificant. For the polymorphism of CFTR1 cystic fibrosis-1 gene, the odds ratio was 0.444, but this finding was not significant. Among patients with the complicated clinical forms of CP, mutations were observed in the PRSS1 cationic trypsinogen gene (c2 = 6.453, p = 0.012) and ADH (c2=14.176, p = 0.001). Conversely, they were not detected in the CFTR-1 gene (c2 = 0.873, p = 0.351), CFTR-2 (c2 was not determined), and SPINK1 (c2 = 0.873, p = 0.351). The polymorphisms of the ADH and PRSS1 genes of cationic trypsinogen were associated with more evident structural changes in the parenchyma and ductal system of the pancreas. They also had a higher likelihood of complications, severe disease course, and a lower efficiency of conservative treatment. The polymorphism of the ADH gene increased the risk of the development of the cystic form of CP (c2 = 5.898, p = 0.016). CONCLUSION: The polymorphism of ADH and cationic trypsinogen genes should be determined and used for the complex diagnosis of CP to specify indications for the surgical treatment of patients with CP.

Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis

1997 ◽  
Vol 113 (4) ◽  
pp. 1063-1068 ◽  
Author(s):  
MC Gorry ◽  
D Gabbaizedeh ◽  
W Furey ◽  
LK Gates ◽  
RA Preston ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Cationic Trypsinogen ◽  
Acute And Chronic Pancreatitis

scholarly journals Motion-Genetic Testing is Useful in the Diagnosis of Nonhereditary Pancreatic Conditions: Arguments Against the Motion

2003 ◽  
Vol 17 (1) ◽  
pp. 53-55 ◽  
Author(s):  
Jonathan A Cohn
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Testing ◽  
Gene Interactions ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Lung Disease ◽  
Increased Risk ◽  
Idiopathic Chronic Pancreatitis ◽  
Cystic Fibrosis Transmembrane ◽  
Compound Heterozygotes

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 bothCFTRalleles (one severely and one mildly affected) are especially susceptible to this disease. Because these compound heterozygotes have sufficient residualCFTRfunction, they do not develop cystic fibrosis lung disease. OnePSTImutation, N34S, independently increases the risk of pancreatitis. Thus, the risk of pancreatitis is greatest among individuals who areCFTRcompound heterozygotes and who also have thePSTImutation. Nonetheless, most people withCFTRandPSTImutations do not develop pancreatitis. This fact indicates that environmental influences and gene-gene interactions also affect pancreatitis risk. AlthoughCFTRandPSTIgenetic 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.

scholarly journals The Differential Role of Human Cationic Trypsinogen (PRSS1) p.R122H Mutation in Hereditary and Nonhereditary Chronic Pancreatitis: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Cheng Hu ◽  
Li Wen ◽  
Lihui Deng ◽  
Chenlong Zhang ◽  
Aurelia Lugea ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Pancreatitis ◽  
Environmental Factors ◽  
Genetic Factors ◽  
Meta Analysis ◽  
Case Control Studies ◽  
Complex Disorder ◽  
Increased Risk ◽  
Cationic Trypsinogen

Background. Environmental factors and genetic mutations have been increasingly recognized as risk factors for chronic pancreatitis (CP). ThePRSS1p.R122H mutation was the first discovered to affect hereditary CP, with 80% penetrance. We performed here a systematic review and meta-analysis to evaluate the associations ofPRSS1p.R122H mutation with CP of diverse etiology.Methods. The PubMed, EMBASE, and MEDLINE database were reviewed. The pooled odds ratio (OR) with 95% confidence intervals was used to evaluate the association of p.R122H mutation with CP. Initial analysis was conducted with all etiologies of CP, followed by a subgroup analysis for hereditary and nonhereditary CP, including alcoholic or idiopathic CP.Results. A total of eight case-control studies (1733 cases and 2415 controls) were identified and included. Overall,PRSS1p.R122H mutation was significantly associated with an increased risk of CP (OR = 4.78[1.13–20.20]). Further analysis showed p.R122H mutation strongly associated with the increased risk of hereditary CP (OR = 65.52[9.09–472.48]) but not with nonhereditary CP, both alcoholic and idiopathic CP.Conclusions. Our study showing the differential role of p.R122H mutation in various etiologies of CP indicates that this complex disorder is likely influenced by multiple genetic factors as well as environmental factors.

Increased risk of idiopathic chronic pancreatitis in cystic fibrosis carriers

2005 ◽  
Vol 26 (4) ◽  
pp. 303-307 ◽  
Author(s):  
Jonathan A. Cohn ◽  
John P. Neoptolemos ◽  
Jinong Feng ◽  
Jin Yan ◽  
Zefei Jiang ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Chronic Pancreatitis ◽  
Increased Risk ◽  
Idiopathic Chronic Pancreatitis

scholarly journals Risk of acute atherosclerotic cardiovascular disease in patients with acute and chronic pancreatitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li-Chin Sung ◽  
Chuen-Chau Chang ◽  
Chao-Shun Lin ◽  
Chun-Chieh Yeh ◽  
Yih-Giun Cherng ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Acute Pancreatitis ◽  
Liver Cirrhosis ◽  
Chronic Pancreatitis ◽  
Control Group ◽  
Atherosclerotic Cardiovascular Disease ◽  
Research Database ◽  
Increased Risk ◽  
History Of ◽  
Acute And Chronic Pancreatitis

AbstractThe association between pancreatitis and acute myocardial infarction or stroke remains incompletely understood. This study aimed to evaluate the long-term risk of acute atherosclerotic cardiovascular disease (ASCVD) in people with acute and chronic pancreatitis. Using research database of Taiwan's National Health Insurance, we identified 2678 patients aged ≥ 20 years with newly diagnosed pancreatitis in 2000–2008. A cohort of 10,825 adults without pancreatitis was selected for comparison, with matching by age and sex. Both cohorts were followed from 2000 to the end of 2013, and incident acute ASCVD was identified during the follow-up period. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of acute ASCVD associated with pancreatitis were calculated. Compared with the comparison cohort, the adjusted HR of acute ASCVD were 1.76 (95% CI 1.47–2.12) and 3.42 (95% CI 1.69–6.94) for people with acute pancreatitis and chronic pancreatitis, respectively. A history of alcohol-related illness (HR 9.49, 95% CI 3.78–23.8), liver cirrhosis (HR 7.31, 95% CI 1.81–29.5), and diabetes (HR 6.89, 95% CI 2.18–21.8) may worsen the risk of acute ASCVD in patients with chronic pancreatitis. Compared with people had no pancreatitis, patients with acute pancreatitis who had alcohol-related illness (HR 4.66, 95% CI 3.24–6.70), liver cirrhosis (HR 4.44, 95% CI 3.05–6.47), and diabetes (HR 2.61, 95% CI 2.03–3.36) were at increased risk of acute ASCVD. However, the cumulative use of metformin was associated with a reduced risk of acute ASCVD in the acute pancreatitis cohort (HR 0.30, 95% CI 0.17–0.50). Compared with the control group, patients with acute or chronic pancreatitis were more likely to have an increased risk of acute ASCVD, while the use of metformin reduced the risk of acute ASCVD. Our findings warrant a survey and education on acute ASCVD for patients with acute and chronic pancreatitis.

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