scholarly journals Mutual Effect of NAT2 rs1799930 (590G>A) Polymorphism and Alcohol Abuse on Risk of Acute Pancreatitis

Author(s):  
T. A. Samgina

Aim. Estimation of the contribution of rs1799930 (590G>A) polymorphism of gene NAT2 to the development of acute alcoholic pancreatitis.Materials and methods. DNA samples were obtained from 547 unrelated patients with acute alcoholic pancreatitis and 573 unrelated individuals without gastrointestinal diseases. A survey selected individuals with the alcohol consumption of >200 g/week pure ethanol two times a week or more during 10 or more years. Genotyping was performed with PCR using TaqMan allelic discrimination assays.Results. No association was observed between the NAT2 allelic rs1799930 (590G>A) polymorphism, risk of acute alcoholic pancreatitis, duration and rate of alcohol consumption. The 590G>A variant of rs1799930 in gene NAT2 correlated with an increased risk of acute alcoholic pancreatitis (odds ratio 2.16; 95% confidence interval 1.13–4.12) under alcohol consumption >200 g/week pure ethanol.Conclusion. The rs1799930 G/A polymorphism of gene NAT2 increases the risk of acute pancreatitis under alcohol consumption >200 g/week pure ethanol.

Author(s):  
Т.А. Самгина ◽  
Д.И. Колмыков ◽  
Г.Н. Мяснянкина ◽  
Ю.Э. Азарова ◽  
Ю.В. Канищев ◽  
...  

Основным фактором риска развития острого алкогольного панкреатита (ОАП) является злоупотребление алкоголем. Алкоголь инициирует экзокринную гиперсекрецию поджелудочной железы, создает предпосылки для повышения давления в протоках. Энзимы проникают в паренхиму, активируют протеолитические ферменты и вызывают аутолиз клеток поджелудочной железы. При избыточном накоплении трипсина в тканях начинается переваривание тканей железы собственными ферментами. SPINK1 - панкреатический секреторный ингибитор трипсина - препятствует преждевременной активации зимогенов. Цель - определить совместный вклад полиморфного локуса rs6580502 гена SPINK1 и злоупотребления алкоголем в развитие острого панкреатита и его осложнений. Образцы ДНК получены от 471 неродственного больного острым небилиарным панкреатитом и 573 неродственных индивидов без заболеваний желудочно-кишечного тракта. Генотипирование выполнено методом ПЦР с дискриминацией аллелей с помощью TaqMan-зондов. Для оценки ассоциаций аллелей и генотипов с риском развития заболевания использовали критерий χ2 и отношение шансов (OR) с 95% доверительными интервалами (CI). Статистический анализ осуществлялся с использованием программы Statistica 6.0 (StatSoft, США). В ходе исследования обнаружена ассоциация генотипа ТТ rs6580502 гена SPINK1 с повышенным риском развития ОАП (corOR (95% CI)= 1,69 (1,22-2,33); р=0,0015R). У носителей генотипа ТТ риск развития ОАП повышали такие факторы риска, как частота употребления алкоголя более 2 раз в неделю (corOR (95% CI) = 1,66 (1,08-2,57); р=0,02R) и объем употребления алкоголя более 200 г в неделю (corOR (95% CI) = 6,04 (1,81-20,17); р= 0,001R). Также была выявлена ассоциация генотипа ТТ с повышенным риском развития отечного панкреатита (corOR (95% CI)= 2.10 (1.44-3.05); p= 1×10-4 R). The main risk factor for the acute non-biliary pancreatitis is alcohol abuse. Alcohol initiates exocrine hypersecretion of the pancreas, creates the prerequisites for increasing pressure in the ducts. Enzymes activate proteolytic enzymes and cause autolysis of pancreatic cells. With an excessive accumulation of trypsin in the tissues, the digestion of the tissues of the gland by its own enzymes begins. SPINK1, a pancreatic secretory trypsin inhibitor, prevents premature activation of zymogens. Aim: to determine the contribution of the rs6580502 polymorphism of the SPINK1 gene and alcohol abuse in the development of acute pancreatitis and its complications. DNA samples obtained from 471 unrelated patients with acute non-biliary pancreatitis and 573 unrelated individuals without gastrointestinal diseases. Genotyping was performed using the PCR method with discrimination of alleles using TaqMan probes. The χ2 criterion and the odds ratio (OR) with 95% confidence intervals (CI) were used to assess the associations of alleles and genotypes of genes with the risk of developing the disease. Statistical analysis was carried out using the Statistica 6.0 software (StatSoft, USA). We found an association of the T/T SPINK1 rs6580502 genotype with an increased risk of developing acute non-biliary pancreatitis (corOR (95% CI)= 1.69 (1.22-2.33); p=0,0015R). In carriers of the TT genotype, the risk of developing SNP was increased by such risk factors as the frequency of drinking more than 2 times per week (corOR (95% CI)= 1,66(1,08-2,57); p=0,02R) and the volume of alcohol consumption more than 200 grams per week (corOR (95% CI)= 6,04(1,81-20,17); p= 0,001R). An association of the T/T genotype with an increased risk of developing edematous pancreatitis was also revealed (corOR (95% CI)= 2.10 (1.44-3.05); Р= 1×10-4 R).


2017 ◽  
Vol 6 (03) ◽  
pp. 5297
Author(s):  
Vedangi Aaren* ◽  
Godi Sudhakar ◽  
Girinadh L.R.S.

In both developed and developing countries, overuse of alcohol is a considered as the major cause of acute and chronic pancreatitis. Prolonged overconsumption of alcohol for 5–10 years typically precedes the initial attack of acute alcoholic pancreatitis. It is observed that only a minority (around 5%) of alcoholics develop pancreatitis. It is now established that the pancreas has the capacity to metabolize ethanol. Previous studies have shown that there are two major pathways of ethanol metabolism, oxidative and non-oxidative. Oxidative ethanol metabolism involves the conversion of ethanol to acetaldehyde, a reaction that is catalysed by aldehyde dehydrogenase (ADH) with contributions from cytochrome P450 enzyme (CYP2E1) and possibly also catalase. Genetic factors regulating alcohol metabolism could predispose in developing alcoholic pancreatitis (AP). We investigated the association of polymorphisms in ADH enzymes with the alcoholic pancreatitis in North coastal Andhra Pradesh. Patients with alcoholic pancreatitis (AP; n = 100), alcoholic controls (AC; n = 100), and healthy controls (HC; n = 100) were included in the study. Blood samples were collected from the subjects in EDTA coated vials. DNA was extracted and genotyping for ADH2 and ADH3 was done by PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism). The products were analysed by gel electrophoresis. The frequency distribution of ADH3*1/*1 genotype was significantly higher in AP group (54%) compared with AC (35%), and HC (42%), and was found to be associated with increased risk of alcoholic pancreatitis. There was no statistically significant difference between the frequency distribution of ADH3*1/*1, ADH3*1/*2, and ADH3*2/*2 genotypes between AC and HC. There was no statistically significant difference between the frequency distribution of ADH2*1/*1, ADH2*1/*2, and ADH2*2/*2 genotypes in AP compared with AC and HC. This study shows that carriers of ADH3*1/*1 individuals consuming alcohol are at higher risk for alcoholic pancreatitis than those with other genotypes such as ADH3*1/*2 and ADH3*2/*2. 


2012 ◽  
Vol 65 (3-4) ◽  
pp. 152-157
Author(s):  
Snezana Tesic-Rajkovic ◽  
Biljana Radovanovic-Dinic ◽  
Tatjana Jevtovic-Stoimenov

Introduction. Alcoholic acute pancreatitis occurs in 10% of alcoholics, who take more than 80g alcohol daily. Different biochemical markers are used to diagnose acute pancreatitis, and some of them may help in establishing etiology of acute pancreatitis. Material and Methods. This study is a prospective review of 21 patients. All patients were hospitalized at the Department for Gastroenterology and Hepatology or at the Department for Surgery of the Clinical Centre of Nis in the period from August 1st 2009 to March 1st 2010 with diagnosis of acute alcoholic pancreatitis. Detailed anamnesis, clinical examination, biochemical analyses and ultrasonography of the upper abdomen were done in all patients. All patients provided data on alcohol abuse. Results. The analysis of the corresponding biochemical parameters revealed a statistically significant correlation between the following values: serum amylase and serum lipase (R=0.964674; p<0.001), cholesterol and triglycerides (R=0.93789; p<0.001), total and direct bilirubin (R=0.857899; p<0.001) and between aspartate aminotransferase and alanine aminotransferase (R=0.824461, p<0.001) in patients with alcoholic acute pancreatitis. In addition, there was a statistically significant correlation between the values of serum amylase and urinary amylase (R=0.582742, p<0.001). Discussion. The analysis of biochemical markers showed that some of them were significant for beforehand diagnosis of alcoholic acute pancreatitis, which is in accordance with other studies. Conclusion Some biochemical parameters can be potential predictors of alcoholic acute pancreatitis (lipase/amylase ratio >2, greater ratio of aspartate aminotransferase/ alanine aminotransferase, enhanced triglycerides and values of mean corpuscular volume.


2013 ◽  
Vol 6 (2) ◽  
pp. 169-179 ◽  
Author(s):  
Milan R. Patel ◽  
Amanda L. Eppolito ◽  
Field F. Willingham

Hereditary pancreatitis shares a majority of clinical and morphologic features with chronic alcoholic pancreatitis, but may present at an earlier age. The term hereditary pancreatitis has primarily been associated with mutations in the serine protease 1 gene (PRSS1) which encodes for cationic trypsinogen. PRSS1 mutations account for approximately 68–81% of hereditary pancreatitis. Mutations in other genes, primarily serine protease inhibitor Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) are also associated with hereditary pancreatitis. While chronic alcoholic pancreatitis may develop in the fourth or fifth decades, patients with hereditary pancreatitis may develop symptoms in the first or second decades of life. Hereditary pancreatitis is diagnosed either by detecting a causative gene mutation or by the presence of chronic pancreatitis in two first-degree or three second-degree relatives, in two or more generations, without precipitating factors and with a negative workup for known causes. Patients with hereditary pancreatitis may have recurrent acute pancreatitis and may develop pancreatic exocrine and endocrine insufficiency. Hereditary pancreatitis may involve premature trypsinogen activation or decreased control of trypsin. Recurrent inflammation can lead to acute pancreatitis and subsequently to chronic pancreatitis with parenchymal calcification. There is a markedly increased risk of pancreatic carcinoma compared with the general population. Patients are often referred for evaluation of pancreatitis, biliary or pancreatic ductal dilatation, jaundice, biliary obstruction, pancreatic duct stone or stricture, pancreatic pseudocysts, and for evaluation for malignancy. Medical treatment includes pancreatic enzyme supplementation, nutritional supplementation, diabetes management, and palliation of pain. Patients should avoid tobacco use and alcohol exposure. Hereditary pancreatitis is reviewed and recommendations for genetic testing are discussed.


2017 ◽  
Vol 5 (2) ◽  
pp. 88-92
Author(s):  
Majharul Haque ◽  
Golam Azam ◽  
Debashis Kumar Sarkar ◽  
Anisur Rahman

Background: Acute pancreatitis is a relatively common disease with variable prevalence in different countries. Different modalities are available for predicting aetiology, severity and outcome of acute pancreatitis with different sensitivity and specificity. Moreover, some are not widely available, some are very expensive. A single, cheap, widely available marker with high sensitivity and specificity is yet to be identified. The present study intends to find out the utility of serum lipase amylase ratio in predicting the aetiology, severity and outcome of acute pancreatitis.Methods: This prospective, observational study was done at the Department of Gastrointestinal Hepatobiliary & Pancreatic Disorders (GHPD), BIRDEM General Hospital, Dhaka, during the period of July 2014 to March 2016. A total of 71 patients with acute pancreatitis were included. Complete blood count, serum amylase, serum lipase, serum calcium, liver function test, renal function test, fasting lipid profile, ultrasonography of whole abdomen, CT scan of upper abdomen and arterial blood gas (ABG) were done in all patients. Statistical analysis was done with SPSS version 16.Results: Among 71 patients, 23(32.4%) were due to biliary cause, 15(21.1%) were due to hypertriglyceridaemia, 4(5.6%) were due to alcohol and 22(31%) were due to unknown causes. 45 (63.4%) patients had mild attack, 10(14.1%) patients had moderate attack and 16(22.5%) patients had severe attack of acute pancreatitis. Out of 71 patients, 17(23.9%) developed complication whereas 54(76.1%) developed no complication. Serum lipase amylase ratio in patients with biliary pancreatitis was 1.40±0.39 and in patients with non-biliary pancreatitis was 2.39±0.84(p <0.001). Again, serum lipase amylase ratio in patients with acute alcoholic pancreatitis was 2.89±0.79 and in patients with non-alcoholic acute pancreatitis was 1.95±0.81 (p=0.002). Serum lipase amylase ratio in patients with acute pancreatitis due to hypertriglyceridaemia was 2.75±0.68 and in patients with acute pancreatitis due to other than hypertriglyceridaemia was 1.62±.65(p< 0.001). This study showed that serum lipase amylase ratio was <2.0 in acute biliary pancreatitis and this ratio was >2.5 in acute alcoholic pancreatitis and in acute pancreatitis due to hypertriglyceridaemia. Serum lipase amylase ratio in patients with mild acute pancreatitis was 1.95±0.89; in patients with moderately severe acute pancreatitis the ratio was 2.37±0.92 and in patients with severe acute pancreatitis, the ratio was 2.22±0.70. The difference of lipase amylase ratio among these groups of patients was not statistically significant (p=0.273). Mean lipase amylase ratio among the patients without complication of acute pancreatitis was 2.03±0.92 whereas this ratio among the patients with complication was 2.17±0.68. This difference of lipase amylase ratio was not statistically significant (p=0.557).Conclusion: Role of serum lipase amylase ratio in predicting the aetiology and severity of acute pancreatitis has been addressed in several recent studies. This study was another attempt to achieve this goal. Predicting the aetiology of acute pancreatitis by such a cheap tool will guide further diagnostic work up and management strategy will avoid unnecessary investigations.Bangladesh Crit Care J September 2017; 5(2): 88-92


Author(s):  
T. A. Samgina ◽  
Yu. E. Azarova ◽  
Yu. V. Kanishchev ◽  
V. A. Lazarenko ◽  
P. M. Nazarenko ◽  
...  

Background. Acute pancreatitis is considered to be an important issue in modern medicine. The phosphatidylethanolamine-N-methyltransferase enzyme plays a significant role in the regulation of lipid metabolism by catalyzing the process of methylation of phosphatidylethanolamine to phosphatidylcholine. These lipids are key components of mitochondrial and cell membranes, providing their fluid and plastic properties and participating in the transport of fats, fatty acids and cholesterol. Along with its function in the synthesis of phosphatidylcholine, the methylation of phosphatidylethanolamine promotes the turnover of S-adenosylmethionine for the synthesis of cysteine and glutathione through transulphurisation. PEMT is a gene encoding the phosphatidylethanolamine-N-methyltransferase enzyme.Aim. To determine the role of PEMT C/T rs12449964 polymorphism in the risk of developing acute pancreatitis and its complications among Russian residents in Central Russia.Materials and methods. Whole blood samples were collected from 502 unrelated patients with acute non-biliary pancreatitis (97 women and 405 men) of Russian nationality who had been admitted to the surgical departments of the city of Kursk from 2015 to 2018, as well as from 513 unrelated individuals of Russian nationality without gastrointestinal diseases (101 women and 412 men). The average age of patients and healthy individuals was 48.9 ± 13.1 and 47.89 ± 12.1 years, respectively. Genomic DNA was isolated by a standard phenol-chloroform extraction method. Genotyping of rs12449964 polymorphism was performed using real-time PCR by allelic discrimination using a CFX96 Bio-Rad Laboratories amplifier (USA) with TaqMan probes and commercial TaqMan SNP Genotyping Assays reagents purchased from Applied Biosystems (USA).Results. The study has shown that the frequency of the C allele and the C/C PEMT C/T rs12449964 genotype was higher in the group of patients with acute pancreatitis, while the C/T genotype was predominant in the control group. C/T — T/T genotypes demonstrated a protective effect on the development of infected pancreatic necrosis, purulent necrotic peripancreatitis and severe acute pancreatitis.Conclusions. The disruption of phosphatidylethanolamine methylation processes increases the sensitivity of cells to oxidative stress, which can lead to the development of acute pancreatitis.


2020 ◽  
Vol 7 (47) ◽  
pp. 2799-2805
Author(s):  
Mohammed Nihad ◽  
Jinu Ibrahim Jamaludeen

BACKGROUND Clinically, the course of all causes of acute pancreatitis is similar; however, inpatients with severe biliary pancreatitis, we can prevent complications with the help of ERCP. Serum L / A ratio of > 2 could help diagnose alcohol as the causative agent1 . Hence, our study aims at assessing the validity in Government Medical College, Thiruvananthapuram, after assessing the specificity and sensitivity of amylase and lipase in alcoholic and non-alcoholic patients separately and lipase amylase ratio as an indicator to distinguish acute alcoholic from non-alcoholic pancreatitis. We also wanted to study the prevalence of pancreatitis in age group of 20 - 40. METHODS This is a diagnostic test evaluation conducted among 92 inpatients of Department of General Surgery selected through consecutive sampling. After randomly selecting patients admitted with a provisional diagnosis of acute pancreatitis, the first investigator administered the consent form, if accepted, examined the patient, evaluated the laboratory parameters. Then these patients were prospectively followed and evaluated. Data are then analysed using Excel spread sheet version 2019 and SPSS software and sensitivity, specificity, prevalence and diagnostic accuracy were determined. RESULTS Among 92 patients, 80 (87 %), 55 (58.8%) and 25 (27.2%) were found to have pancreatitis, alcoholic and non-alcoholic causes respectively. 35 (38 %) patients were in the age group of 31 – 35 years. It was found that lipase has 94.55 % & 91.6 % sensitivity and specificity in alcoholic and 84 % & 91.6 % sensitivity and specificity in non-alcoholic pancreatitis patients, respectively, and amylase has 69 % & 91.67 % sensitivity and specificity in alcoholic and 72 % & 91.67 % sensitivity and specificity in non-alcoholic pancreatitis respectively. CONCLUSIONS Serum amylase and lipase are inevitable investigations with good sensitivity and specificity in the diagnosis of acute pancreatitis. Lipase amylase ratio >2 is diagnostic of alcoholic pancreatitis. KEYWORDS Acute Pancreatitis, Acute Alcoholic Pancreatitis, Acute Non-Alcoholic Pancreatitis, Specificity of Lipase and Amylase, Lipase Amylase Ratio


2005 ◽  
Vol 123 (6) ◽  
pp. 289-291 ◽  
Author(s):  
Clayton Rocha Lara Carrera ◽  
Leandro Mont'Alverne Pierre ◽  
Flavio Mac Cord Medina ◽  
Paulo de Tarso Ponte Pierre-Filho

CONTEXT: Purtscher-like retinopathy with bilateral loss of vision is a rare and severe complication that may follow acute pancreatitis. CASE REPORT: The case of a 35-year-old patient with acute alcoholic pancreatitis who developed sudden loss of visual acuity is described. The ophthalmoscopic examination revealed diffuse retinal whitening of the posterior pole with confluent cotton-wool spots. Fluorescein angiogram showed retinal arteriolar occlusion. The findings were compatible with Purtscher-like retinopathy. Computed tomography of the abdomen demonstrated enlarged liver and pancreas with edema and inflammation. The pathogenesis of this form of retinopathy still remains uncertain and there is no specific treatment available.


Sign in / Sign up

Export Citation Format

Share Document