scholarly journals CFTR F508del mutation and 5T allele in patients with chronic pancreatitis and pancreatic adenocarcinoma

2011 ◽  
Vol 58 (3) ◽  
pp. 43-47
Author(s):  
Aleksandra Nikolic ◽  
Jelena Dinic ◽  
Dragica Radojkovic ◽  
Snezana Lukic ◽  
Dragan Popovic ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Chronic Pancreatitis ◽  
Pancreatic Adenocarcinoma ◽  
Genetic Variants ◽  
Cftr Gene ◽  
Common Mutation ◽  
Healthy Individuals ◽  
Pancreatic Diseases ◽  
Pancreatic Disorders ◽  
Pancreatic Pathology

Introduction: Mutations in the CFTR gene may be associated with various types of pancreatic pathology and result in higher risk of pancreatic disorders. While delta F508 is the most common mutation in cystic fibrosis patients, the allel 5T is associated with atypical forms of cystic fibrosis. Study aim: The aim of this study was to establish the frequencies of F508del mutation and 5T allele in the CFTR gene in patients with chronic pancreatitis and pancreatic cancer, as well as to investigate whether these genetic variants represent risk factors for pancreatic diseases. Study methods: The study has encompassed 50 patients with chronic pancreatitis and 50 patients with pancreatic adenocarcinoma, as well as 124 healthy individuals. The analysis of F508del mutation and alleles 5T, 7T and 9T of the polythymidine tract was performed on DNA extracted from periferal blood by PCR-mediated site-direted mutagenesis (PSM) method. Results: The frequency of F508del mutation in the group of patients with chronic pancreatitis (3.0%) was significantly increased (p=0.032) in comparison to the group of healthy individuals (0.4%), while other analyzed differences were not statistically significant. Conclusion: The results of this study indicate that F508del mutation in the CFTR gene respresents a risk factor for the development of chronic pancreatitis.

scholarly journals GSTP1 Ile105Val Polymorphism in Serbian Patients with Pancreatic Diseases

2011 ◽  
Vol 30 (2) ◽  
pp. 121-125 ◽  
Author(s):  
Aleksandra Nikolić ◽  
Marija Stanković ◽  
Ivan Nišević ◽  
Snežana Lukić ◽  
Marina Anđelić-Jelić ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Pancreatic Cancer ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Pancreatitis ◽  
Healthy Individuals ◽  
Pancreatic Diseases ◽  
Gstp1 Ile105val ◽  
Pancreatic Pathology

GSTP1 Ile105Val Polymorphism in Serbian Patients with Pancreatic DiseasesThe aim of the current preliminary case-control study was to identify glutathione S-transferase P1 (GSTP1) Ile105Val allele and genotype frequency and to evaluate its impact on susceptibility to pancreatic diseases in a Serbian population. This study has encompassed 157 patients with three major types of chronic pancreatic pathology: 47 with pancreatic cancer, 50 with chronic pancreatitis and 60 with type 2 diabetes mellitus, as well as 107 healthy individuals. The presence of GSTP1 Ile105Val polymorphism was analyzed using a PCR-RFLP method. Allele 105Val was less frequent in patients with pancreatic cancer (24.5%) and chronic pancreatitis (24.0%) and slightly more frequent in patients with type 2 diabetes mellitus (31.7%) in comparison to healthy individuals (29.9%), but the differences were not statistically significant. Distribution of Ile105Val polymorphism genotypes differed between the analyzed groups, but differences were also not statistically significant. There are only a few studies regarding the role of GSTP1 Ile105Val polymorphism in pancreatic diseases and their results are inconsistent. The significance of GSTP1 Ile105Val polymorphism for pancreatic pathology remains unclear and further studies are needed in order to elucidate its role in pancreatic diseases.

Clinical and genetic characteristics of rare pathogenic variants of the CFTR gene in Russian patients with cystic fibrosis

2021 ◽  
Vol 31 (2) ◽  
pp. 148-158
Author(s):  
A. Yu. Voronkova ◽  
Yu. L. Melyanovskaya ◽  
N. V. Petrova ◽  
T. A. Adyan ◽  
E. K. Zhekaite ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Variants ◽  
Pancreatic Insufficiency ◽  
Protein Energy Malnutrition ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Cftr Gene ◽  
Genetic Characteristics ◽  
Missense Variants ◽  
Pathogenic Variants

The variety of clinical manifestations of cystic fibrosis is driven by the diversity of the CFTR gene nucleotide sequence. Descriptions of the clinical manifestations in patients with the newly identified genetic variants are of particular interest.The aim of this study was to describe clinical manifestations of the disease with the newly identified genetic variants.Methods. Data from Registry of patients with cystic fibrosis in the Russian Federation (2018) were used. The data review included three steps — the search for frequent mutations, Sanger sequencing, and the search for extensive rearrangements by MLPA. 38 pathogenic variants were identified that were not previously described in the international CFTR2 database. We selected and analyzed full case histories of 15 patients with 10 of those 38 pathogenic variants: p.Tyr84*, G1047S, 3321delG, c.583delC, CFTRdele13,14del18, CFTRdele19-22, c.2619+1G>A, c.743+2T>A, p.Glu1433Gly, and CFTRdel4-8del10-11.Results. A nonsense variant p.Tyr84* was found in 5 patients (0.08 %). Two missense variants c.3139G>A were found in 2 siblings (0.03 %). The c.4298A>G was found in 1 patient. Other variants were detected in a single patient (0.02 %) each. They included two variants of a deletion with a shift of the reading frame 3321delG and c.583delC, two splicing disorders c.2619+1G>A and c.743+2T>A, three extended rearrangements CFTRdele19-22, CFTRdele13,14del18, and CFTRdel4-8del10-11. The last two variants include 2 rearrangements on one allele, which cause the severe course in two young children. 8 of the 10 variants are accompanied by pancreatic insufficiency (PI). Among patients with p.Tyr84*, one had ABPA, one had liver transplantation, and all had Pseudomonas aeruginosa infection. Nasal polyps were diagnosed in 2 patients with p.Tyr84*, 1 with G1047S, 1 with CFTRdel4-8del10-11, and 1 patient with 3321delG, who also had osteoporosis and cystic fibrosis-related diabetes (CFRD). 2 patients with PI with 3321delG and CFTRdel4-8del10-11 genetic variants, and 1 with PI with p.Glu1433Gly genetic variant had severe protein-energy malnutrition (PEM).Conclusion. Clinical manifestations of previously undescribed CFTR genetic variants were described. 5/10 genetic variants should be attributed to class I, 3/10 – to class 7 of the function classification of pathogenic CFTR gene variants associated with transcription and translation disruptions. Class of the identified missense variants c.3139G>A and c.4298A>G has not been established and requires further functional, cultural, and molecular genetic studies.

scholarly journals Features of spectrum of pathogenic genetic variants of the CFTR gene in patients with cystic fibrosis from Krasnoyarsk territory

2020 ◽  
Vol 15 (2) ◽  
Author(s):  
Natalia Anatolievna Ilyenkova ◽  
Vladimir Viktorovich Chikunov ◽  
Elena Ivanovna Kondratieva
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Variants ◽  
Cftr Gene

Diagnostic criteria of pancreatic pathology.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16696-e16696
Author(s):  
Irina V. Neskubina ◽  
Elena M. Frantsiyants ◽  
Irina V. Kaplieva ◽  
Ekaterina I. Surikova ◽  
Valeria A. Bandovkina ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Pancreatic Adenocarcinoma ◽  
Neuroendocrine Tumors ◽  
Malignant Tumors ◽  
Lymphatic Vessels ◽  
Blood Levels ◽  
Pancreatic Neuroendocrine Tumors ◽  
Pancreatic Pathology ◽  
Diagnostic Criterion

e16696 Background: Vascular endothelial growth factors (VEGF) and their receptors provide malignant tumors with new blood and lymphatic vessels. However, it is unknown whether their level in the blood can help to determine the tumor nature or to distinguish malignant pathology from chronic organ inflammation. The purpose of the study was to reveal the dynamics of VEGF in the blood of patients with chronic pancreatitis and pancreatic cancer. Methods: The study included male patients with chronic pancreatitis (n = 9), pancreatic adenocarcinoma T1-3N0-1M0 (n = 10) and pancreatic neuroendocrine tumors T1-3N0-1M0 (n = 12) before treatment. Healthy males (n = 21) were controls. Blood levels of VEGF-A, VEGF-C, VEGF-R1 and VEGF-R3 were determined by ELISA using standard test systems (Cusabio, China). Results: VEGF-A in the blood of patients with pancreatic cancer increased: in adenocarcinoma by 2.6 times, in neuroendocrine tumors by 1.7 times (p < 0.05), while chronic pancreatitis was characterized with reduced VEGF-A in the blood – 2.2 times lower than in healthy people. Serum concentration of VEGF-C increased only in patients with adenocarcinoma – 1.3 times higher than the norm (p < 0.05). The amount of VEGF-R1 and VEGF-R3 receptors increased in the blood of patients with chronic pancreatitis (by 2.2 and 1.6 times respectively, p < 0.05) and pancreatic neuroendocrine tumors (2.2 and 1.3 times, p < 0.05). Conclusions: The rise of VEGF-A in the blood is a sign of malignant pancreatic pathology; its combination with the accumulation of VEGF-C in the blood is a diagnostic criterion for pancreatic adenocarcinoma, and a combination with an increase in VEGF-R1 and VEGF-R3 is a diagnostic criterion for pancreatic neuroendocrine tumors. In contrast, chronic pancreatitis is characterized by reduced VEGF-A together with the increase in both types of receptors in the blood.

Secondary Forms of Diabetes Mellitus

2019 ◽  
Author(s):  
Ildiko Lingvay ◽  
Philip Raskin
Keyword(s):  
Diabetes Mellitus ◽  
Cystic Fibrosis ◽  
Chronic Pancreatitis ◽  
Gestational Diabetes ◽  
Genetic Disorders ◽  
Genetic Mutations ◽  
Chemical Agents ◽  
Pancreatic Disorders

Secondary forms of diabetes mellitus are those cases of diabetes mellitus that have a specific identifiable cause and do not meet the diagnostic criteria for type 1, type 2, or gestational diabetes. This review discusses the etiology, pathogenesis, diagnosis, management, complications, and prognosis of these forms, which include diabetes mellitus occurring as a result of pancreatic disorders; endocrinopathies; drugs, chemical agents, or toxins; and genetic mutations or syndromes. Tables list the endocrinopathies; the drug, chemicals, and toxins; and the genetic disorders causing secondary forms of diabetes mellitus. This review contains 3 tables and 15 references. KeyWords: chronic pancreatitis, pancreatic carcinoma, cystic fibrosis, hemochromatosis, malnutrition, diabetic ketoacidosis or symptomatic hyperglycemia or hypoglycemia

scholarly journals Analysis of the CFTR gene in Venezuelan cystic fibrosis patients, identification of six novel cystic fibrosis-causing genetic variants

2016 ◽  
pp. 33 ◽  
Author(s):  
Karen Sánchez ◽  
Elizabeth De Mendonca ◽  
Xiorama Matute ◽  
Ismenia Chaustre ◽  
Marlene Villalon ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Variants ◽  
Cftr Gene

scholarly journals Functional characteristics of L1156F-CFTR associated with alcoholic chronic pancreatitis in Japanese

2015 ◽  
Vol 309 (4) ◽  
pp. G260-G269 ◽  
Author(s):  
Shiho Kondo ◽  
Kotoyo Fujiki ◽  
Shigeru B. H. Ko ◽  
Akiko Yamamoto ◽  
Miyuki Nakakuki ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Chronic Pancreatitis ◽  
Normal Subjects ◽  
Cftr Gene ◽  
Xenopus Laevis Oocytes ◽  
Transport Activity ◽  
Coding Region ◽  
Functional Characteristics ◽  
Alcoholic Chronic Pancreatitis ◽  
Exchange Activity

Although cystic fibrosis is rare in Japanese, measurement of sweat Cl− has suggested mild dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR) in some patients with chronic pancreatitis. In the present study, we have investigated the association of CFTR variants and chronic pancreatitis in Japanese and the functional characteristics of a Japanese- and pancreatitis-specific CFTR variant, L1156F. Seventy patients with alcoholic chronic pancreatitis, 18 patients with idiopathic chronic pancreatitis, and 180 normal subjects participated. All exons and their boundaries and promoter region of the CFTR gene were sequenced. Human embryonic kidney-293 cells were transfected with three CFTR variants (M470V, L1156F, and M470V+L1156F), and the protein expression was examined. Xenopus laevis oocytes were injected with the CFTR variants, and bicarbonate (HCO3−) transport activity was examined. CFPAC-1 cells were transfected with the CFTR variants and Cl−/HCO3− exchange activity was examined. Six variants (E217G, I556V, M470V, L1156F, Q1352H, and R1453W) were identified in the coding region of the CFTR gene. Cystic fibrosis-causing mutations were not found. The allele frequencies of L1156F and Q1352H in alcoholic chronic pancreatitis (5.0 and 7.9%) were significantly ( P < 0.01) higher than those in normal subjects (0.6 and 1.9%). L1156F was linked with a worldwide CFTR variant, M470V. Combination of M470V and L1156F significantly reduced CFTR expression to ∼60%, impaired CFTR-mediated HCO3−/Cl− transport activity to 50–60%, and impaired CFTR-coupled Cl−/HCO3− exchange activity to 20–30%. The data suggest that the Japanese-specific CFTR variant L1156F causes mild dysfunction of CFTR and increases the risk of alcoholic chronic pancreatitis in Japanese.

scholarly journals Prospective observational study on pancreatic duct system diversity in different pancreatic diseases

2017 ◽  
Vol 4 (10) ◽  
pp. 3330
Author(s):  
Navjot Singh Brar ◽  
Rajbir Singh Bajwa
Keyword(s):  
Acute Pancreatitis ◽  
Chronic Pancreatitis ◽  
Pancreatic Duct ◽  
Pancreatic Head ◽  
Lemon Juice ◽  
Imaging Modalities ◽  
Cystic Neoplasm ◽  
Pancreatic Diseases ◽  
Ductal System ◽  
Pancreatic Disorders

Background: Pancreatology and pancreatic surgery was developed on the basis of increase in knowledge of anatomy and physiology of the pancreas in the beginning of the 20th century. Although our knowledge of pancreatic head anatomy has increased, anatomical data characterizing the pancreatic ductal system remain limited. Furthermore, the relation of pancreatic ductal system anomalies and different pancreatic disorders remain to be evaluated.Methods: The present study was conducted in Department of Paediatric, Sri Guru Ram Das Institute of Medical Sciences and Research, Vallah, Sri Amritsar from August 2014 to November 2016. Total 50 subjects were included. Study was done with aim to study cases clinically and segregate cases with pancreatic disorder which need evaluation by special imaging modalities and surgical management, to compare the nature of information obtained from various modalities to study various corollaries of modern imaging study, to study whether the information from various imaging modalities are complimentary, competitive and to study pancreatic ductal structure in different pancreatic diseases.Results: In the present study, we have a total of 50 patients. Among them 25 (50%) suffer from chronic pancreatitis, 13 (26%) from acute pancreatitis, 6 (12%) from periampullary carcinoma, 3 (6%) from carcinoma head of the pancreas, 1 (2%) from pancreatic ascites following acute pancreatitis, 1 (2%) from annular pancreas and 1 (2%) from cystic neoplasm of pancreas. These patients were investigated by transabdominal USG, MDCT scan, ERCP and conventional and stimulated MRCP to study the pancreatic duct diversities in different pancreatic diseases and the advantage of lemon juice stimulated MRCP over conventional MRCP.Conclusions: Pancreatic disorders were most frequently seen in male patients. Age group between 31 to 50 years were mostly suffering from inflammatory disorders like acute and chronic pancreatitis. The frequency of malignant condition was increased after 50 years of age. Most common pancreatic disorder in our study was chronic pancreatitis. Trans-abdominal USG was found to be very useful initial investigation for the evaluation of pancreatic duct morphology. Best investigation for malignant pancreatic condition was MDCT following pancreatic protocol.

scholarly journals Diagnostic contribution of molecular analysis of the cystic fibrosis transmembrane conductance regulator gene in patients suspected of having mild or atypical cystic fibrosis

2013 ◽  
Vol 39 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Vinícius Buaes Dal'Maso ◽  
Lucas Mallmann ◽  
Marina Siebert ◽  
Laura Simon ◽  
Maria Luiza Saraiva-Pereira ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Molecular Analysis ◽  
Clinical Characteristics ◽  
Genetic Diagnosis ◽  
Cftr Gene ◽  
Sweat Test ◽  
Common Mutation ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane

OBJECTIVE: To evaluate the diagnostic contribution of molecular analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients suspected of having mild or atypical cystic fibrosis (CF). METHODS: This was a cross-sectional study involving adolescents and adults aged ≥ 14 years. Volunteers underwent clinical, laboratory, and radiological evaluation, as well as spirometry, sputum microbiology, liver ultrasound, sweat tests, and molecular analysis of the CFTR gene. We then divided the patients into three groups by the number of mutations identified (none, one, and two or more) and compared those groups in terms of their characteristics. RESULTS: We evaluated 37 patients with phenotypic findings of CF, with or without sweat test confirmation. The mean age of the patients was 32.5 ± 13.6 years, and females predominated (75.7%). The molecular analysis contributed to the definitive diagnosis of CF in 3 patients (8.1%), all of whom had at least two mutations. There were 7 patients (18.9%) with only one mutation and 26 patients (70.3%) with no mutations. None of the clinical characteristics evaluated was found to be associated with the genetic diagnosis. The most common mutation was p.F508del, which was found in 5 patients. The combination of p.V232D and p.F508del was found in 2 patients. Other mutations identified were p.A559T, p.D1152H, p.T1057A, p.I148T, p.V754M, p.P1290P, p.R1066H, and p.T351S. CONCLUSIONS: The molecular analysis of the CFTR gene coding region showed a limited contribution to the diagnostic investigation of patients suspected of having mild or atypical CF. In addition, there were no associations between the clinical characteristics and the genetic diagnosis.

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