The Role of Phosphatidylethanolamine-N-methyltransferase (PEMT) Gene rs12449964 Polymorphism in the Development of Acute Pancreatitis and its Complications

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.

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Features of the formation of the St. Petersburg agglomeration by the beginning of the XX century

E3S Web of Conferences ◽

10.1051/e3sconf/202016405009 ◽

2020 ◽

Vol 164 ◽

pp. 05009

Author(s):

Sergey Sementsov ◽

Svetozar Zavarikhin ◽

Yuryi Kurbatov ◽

Yuryi Pukharenko

Keyword(s):

Urban Planning ◽

Significant Role ◽

Communication Analysis ◽

Garden Cities ◽

Central Russia ◽

Environmental Transport ◽

Spatially Extended ◽

The Baltic ◽

The City

The study of the Russian historical St. Petersburg agglomeration at all stages from its foundation (from 1703) until the final imperial stage (1917) required the use of complex functional, urban-planning and landscape, socio-economic, environmental, transport and communication analysis on the basis of data from archives, historical cartography and iconography. The main results were the conclusions that during the XVIII - early XX centuries, there was a crystallization of a huge agglomeration around the city of St. Petersburg, which included three belts: “external”, “middle”, “nearby”, which spatially extended from Yaroslavl (in Central Russia) to Riga (in the Baltic). The paper discusses the features of the formation of the “nearby belt” of agglomeration in the initial (1703 - January 1725) and in the final (1901-1916) development periods. The study revealed a significant role of special types of objects in these processes - estates of the aristocratic society and “garden cities” that provided a belt (around St. Petersburg and the largest settlements and complexes), linear (along radial and ring highways), and nodal (around individual large settlements) construction, spreading in the latitudinal direction from Narva and Ivangorod to the mouth of the Syas river, and in the meridian direction - from Vyborg to the city of Luga. Within the boundaries of this agglomeration zone, four sub-agglomerations had begun to emerge since the 1710s and have fully formed by the 1910s. The materials of the paper can be useful both for historians of urban planning and for modern urbanists.

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The role of some xenobiotic biotransformation genes snp in the development of acute pancreatitis

Bulletin of Russian State Medical University ◽

10.24075/brsmu.2020.008 ◽

2020 ◽

pp. 34-39

Author(s):

T.A. Samgina ◽

P.M. Nazarenko ◽

A.V. Polonikov ◽

V.A. Lazarenko

Keyword(s):

Acute Pancreatitis ◽

Pancreatic Necrosis ◽

Gastrointestinal Diseases ◽

Taqman Probes ◽

History Of ◽

Xenobiotic Biotransformation ◽

Genetically Determined ◽

Genotype A

Genetically determined features of the xenobiotic biotransformation system play an important role in the development of acute pancreatitis (AP) and its complications. The aim of this study was to assess the contribution of 3 SNPs (CYP1A1 -462 T>C rs1048943, CYP2E1 -1293 G>C rs3813867 and ABCB1 -3435 G>A rs1045642) to the development of AP and its complications. DNA samples were collected from 547 unrelated patients with AP (154 women and 393 men; mean age 48.9 ± 13.1 years) undergoing therapy at surgery departments of Kursk and 573 unrelated individuals without gastrointestinal diseases (161 women and 412 men; mean age 47.8 ± 12.1 years). The polymorphisms were genotyped by PCR using TaqMan probes for allele discrimination. Infected pancreatic necrosis (IPN) was observed in 97 patients; 101 patients developed a pseudocyst (PC); 111 patients had a peripancreatic necrosis (PN). AP was the most common in the carriers of the А allele in ABCB1 G>A (rs1045642) (p = 0.0008). The carriers of the G/G genotype rarely developed both AP (p = 5·10–4) and its complications: IPN (p = 0.03R), PN (p = 0.036R), PC (p = 0.04R). The carriers of the G/C–C/C CYP2E1 G>C (rs3813867) genotypes who had no long-term history of alcohol abuse rarely developed AP (p = 0.03). The carriers of the G/C CYP2E1 (rs3813867) genotype tended to develop pseudocysts (p = 0.05OD). AP was more frequently complicated by IPN (p = 0.009R), PN (p = 0.003R) and PC (p = 0.003D) in the carriers of the C/C CYP1A1 T>C (rs1048943) genotype. A milder course of AP was typical for the carriers of the G/G ABCB1 G>A (rs1045642) genotype; a more severe course was characteristic of the carriers of the C/C CYP1A1 T>C (rs1048943) genotype.

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The Antioxidant Profiles, Lysosomal and Membrane Enzymes Activity in Patients with Acute Pancreatitis

Mediators of Inflammation ◽

10.1155/2014/376518 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 11

Author(s):

Halina Milnerowicz ◽

Radosław Bukowski ◽

Monika Jabłonowska ◽

Milena Ściskalska ◽

Stanisław Milnerowicz

Keyword(s):

Oxidative Stress ◽

Acute Pancreatitis ◽

Healthy Subjects ◽

Control Group ◽

Activity Levels ◽

First Line ◽

Course Of Disease ◽

Antioxidative Status ◽

Gpx Activity

Oxidative stress and inflammatory mediators, such as IL-6, play an important role in the pathophysiology of acute pancreatitis. The study was aimed to assess the degree of the pro/antioxidative imbalance and estimate which antioxidant plays a role in the maintenance of pro/antioxidative balance during acute pancreatitis. The study was investigated in the blood of 32 patients with acute pancreatitis and 37 healthy subjects. IL-6 concentration as early marker of inflammation was determinated. The intensity of oxidative stress was assessed by TBARS concentration. To investigate antioxidative status, the GPx and Cu/Zn SOD activities and the levels of GSH, MT, SH groups, and TRAP were measured. The concentrations of Cu and Zn as ions participating in the maintenance of antioxidant enzymes stability and playing a role in the course of disease were determinated. The activities of GGT, AAP, NAG, andβ-GD as markers of tissue damage were also measured. An increase in IL-6 concentration, which correlated with Ranson criteria, and an increase in GPx activity, levels of MT, TBARS, or GGT, and NAG activities in patients group compared to healthy subjects were demonstrated. A decrease in GSH level in patients group compared to control group was noted. The studies suggest that GPx/GSH and MT play the role of the first line of defence against oxidative stress and pro/antioxidant imbalance in the course of acute pancreatitis.

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Role of diffusion-weighted MR imaging in diagnosis of acute pancreatitis

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-020-00242-x ◽

2020 ◽

Vol 51 (1) ◽

Author(s):

Hanan M. Abuzeid ◽

Aya Yassin ◽

Omar F. Kamel ◽

Kareem A. Sabry

Keyword(s):

Magnetic Resonance Imaging ◽

Acute Pancreatitis ◽

Magnetic Resonance ◽

Control Group ◽

Resonance Imaging ◽

Adc Value ◽

Diffusion Weighted ◽

Adc Values ◽

Weighted Magnetic Resonance Imaging

Abstract Background The role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the diagnosis of acute pancreatitis is assessed in this study by measuring the apparent diffusion coefficient (ADC) values in acute pancreatitis and comparing them with a control group. The aim of this study is to compare those two groups thus supporting the diagnosis of this disease. Sixteen patients with acute pancreatitis and 16 control participants underwent diffusion-weighted imaging with b values of 0, 200, and 800. ADC maps were generated from the DW-MRI and ADC values, which were calculated for the pancreas, and the results of the two groups of patients were compared. Results The mean pancreatic ADC value in the acute pancreatitis group (1.15 10(−3) mm(2)/s ± 0.28) was significantly lower than in the normal group (1.6 10−3 mm(2)/s ± 0.2). A threshold ADC value of 1.38 10−3 mm(2)/s yielded 81.25%, specificity of 93.75%, positive predictive value of 92.9%, negative predictive value of 83.3%, and accuracy of 91.8%. Pancreatic ADC values were significantly lower in patients with acute pancreatitis than in the control group. Conclusion Diffusion-weighted magnetic resonance imaging could be an important supportive tool in the diagnosis of acute pancreatitis.

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

Russian Journal of Gastroenterology Hepatology Coloproctology ◽

10.22416/1382-4376-2020-30-6-40-44 ◽

2020 ◽

Vol 30 (6) ◽

pp. 40-44

Author(s):

T. A. Samgina

Keyword(s):

Acute Pancreatitis ◽

Alcohol Consumption ◽

Mutual Effect ◽

Gastrointestinal Diseases ◽

Alcoholic Pancreatitis ◽

Allelic Discrimination ◽

Pure Ethanol ◽

Taqman Allelic Discrimination ◽

Increased Risk ◽

Acute Alcoholic Pancreatitis

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.

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TPH1 gene polymorphism rs211105 influences serotonin and tryptophan hydroxylase 1 concentrations in acute pancreatitis patients

10.21203/rs.3.rs-567244/v2 ◽

2021 ◽

Author(s):

Jadwiga Snarska ◽

Ewa Fiedorowicz ◽

Dominika Rozmus ◽

Konrad Wroński ◽

Maria Latacz ◽

...

Keyword(s):

Acute Pancreatitis ◽

Metabolic Pathway ◽

Tryptophan Hydroxylase ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Serotonin Synthesis ◽

Single Nucleotide ◽

Factors Affecting ◽

Rate Limiting

Abstract Background The role of serotonin and its metabolic pathway in proper functioning of the pancreas has not been thoroughly investigated yet in acute pancreatitis (AP) patients. Tryptophan hydroxylase (TPH) as the rate-limiting enzyme of serotonin synthesis has been considered for possible associations in various diseases. Single-nucleotide polymorphisms (SNPs) in TPH genes have been already described in associations with psychiatric and digestive system disorders. This study aimed to explore the association of a rs211105 (T/G) polymorphism in TPH1 gene with tryptophan hydroxylase 1 concentrations in blood serum in a population of acute pancreatitis patients, and to investigate this association with acute pancreatitis susceptibility. Results Our data showed an association between the presence of the T allele at the position rs211105 (OR = 2.47, 95% CI: 0.94-6.50, p = 0.06) under conditions of a decreased AP incidence. For TT and GT genotypes in the control group, the lowest concentration of TPH was associated with higher serotonin levels (TT: Rs=-0.415, p=0.0018; GT: Rs=-0,457, p=0.0066), while for the AP group the highest levels of TPH among the TT genotype were associated with lower levels of serotonin (TT: Rs=-0.749, p<0.0001, and in the GG genotype higher levels of TPH were associated with higher levels of serotonin (GG: Rs=-0.738, p=0.037). Conclusions Here, a new insight in the potential role of a selected genetic factor in pancreatitis development was shown. Not only the metabolic pathway of serotonin, but also factors affecting serotonin synthesis may be interesting and important points in acute pancreatitis.

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Novel data about association of the functionally significant polymorphisms of the MMP-9 gene with exfoliation glaucoma in the Caucasian population of Central Russia

Ophthalmic Research ◽

10.1159/000512507 ◽

2020 ◽

Author(s):

Dina Starikova ◽

Irina Ponomarenko ◽

Evgeny Reshetnikov ◽

Volodymyr Dvornyk ◽

Mikhail Churnosov

Keyword(s):

Regulatory Protein ◽

Additive Model ◽

Caucasian Population ◽

Control Group ◽

Regulatory Motifs ◽

Exfoliation Glaucoma ◽

Central Russia ◽

Increased Risk ◽

Evolutionarily Conserved

Aim: This study aimed to investigate the role of functionally significant polymorphisms of the MMP-1, MMP-3, and MMP-9 genes in the development of exfoliation glaucoma (XFG) in the Caucasian population of Central Russia. Methods: The study sample consisted of 724 participants, including 328 patients with XFG and 396 individuals in the control group. The participants were of Russian ethnicity (self-reported) born in Central Russia. The participants were genotyped at eight functionally significant polymorphisms of the MMP genes (rs3918242, rs3918249, rs17576, rs3787268, rs2250889, rs17577 MMP9, rs679620 MMP3, and rs1799750 MMP1). The association analysis was performed using logistic regression. Two polymorphisms, which were associated with XFG, and 12 polymorphisms linked to them (r2≥0.8) were analyzed for their functional significance in silico. Results: Allele C of rs3918249 MMP9 was associated with XFG according to the additive model (OR = 0.75, 95% CI 0.56-0.93, pperm = 0.015), and allele G of the rs2250889 MMP9 locus was associated with XFG according to the additive (OR = 1.59, 95% CI 1.10-2.29, pperm = 0.013) and dominant (OR = 1.68, 95% CI 1.11- 2.56, рperm = 0.016) models. Two XFG-associated loci of the MMP9 gene и 12 SNPs linked to them had a significant regulatory potential (they are located in the evolutionarily conserved regions, promoter and enhancer histone marks, the DNAase- hypersensitivity regions, a region binding to regulatory protein and a region of regulatory motifs) and may influence the expression of 13 genes and alternative splicing of four genes in various tissues and organs related to the pathogenesis of XFG. Conclusion: Allele C rs3918249 MMP9 decreased risk for XFG (OR = 0.75) and allele G of the rs2250889 MMP9 locus increased risk for XFG (OR = 1.59-1.68) in the Caucasian population of Central Russia.

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The role of MGMT polymorphisms (Rs12917 and Rs11016879) in head and neck cancer risk and prognosis

Acta Biochimica Polonica ◽

10.18388/abp.2017_1613 ◽

2018 ◽

Vol 65 (1) ◽

pp. 87-92 ◽

Cited By ~ 1

Author(s):

Paweł Kiczmer ◽

Alicja Prawdzic Seńkowska ◽

Joanna Katarzyna Strzelczyk ◽

Błażej Szydło ◽

Krzysztof Biernacki ◽

...

Keyword(s):

Head And Neck ◽

Dna Methyltransferase ◽

Nodal Metastasis ◽

Control Group ◽

Allelic Discrimination ◽

Test Analysis ◽

Methylguanine Dna Methyltransferase ◽

Increased Risk ◽

Risk Of Cancer

Head and neck squamous cell carcinoma (HNSCC) is one of the leading cancers by incidence worldwide. The risk of these cancers is strictly associated with alkylation factors present in tobacco smoke. The crucial role in preventing DNA alkylation is played by O6-methylguanine-DNA methyltransferase (MGMT). Dysfunction or lack of MGMT is associated with an increased risk of cancer. The aim of the study was to assess the influence of MGMT polymorphisms: Rs12917 and Rs11016879 on HNSCC risk and course. The study consisted of 42 HNSCC patients and 58 healthy individuals. Case samples were taken from resected tumour tissue. The control group comprised samples of epithelial cells collected from mucous membranes using swabs. To analyse the SNPs we performed Real-Time PCR. DNA samples were genotyped by employing the 5' nuclease assay for allelic discrimination using TaqMan SNP Genotyping Assays. The significance between distributions of genotypes and alleles was tested using the Pearson’s χ2 test analysis. The MGMT Rs12917 TT genotype was observed only in the HNSCC patients. In case of Rs11016879 no increase in the risk was observed (p>0.05). However, we noted higher risk of nodal metastasis in Rs11016879 homozygotes [OR=10.67 (95% CI=0.36-23.93), p=0.03]. Our findings suggest that MGMT gene polymorphisms may play an important role in risk and prognosis of HNSCC. Mechanisms leading to MGMT enzymatic defect remain unknown and hence further studies need to be carried out into this topic.

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A STUDY ON ROLE OF OCTREOTIDE ON OUTCOME OF PATIENTS WITH ACUTE PANCREATITIS

10.36106/gjra/4303162 ◽

2020 ◽

pp. 22-24

Author(s):

Vishal Lodha ◽

Rajesh Sonsale ◽

Sandip Jadhav

Keyword(s):

Acute Pancreatitis ◽

Hospital Stay ◽

Case Control Study ◽

Case Control ◽

Control Group ◽

Care Hospital ◽

Group A ◽

Group B ◽

Control Study

Introduction: Mild pancreatitis is a self limiting disease, while morbidity and mortality is considerably high in cases of severe necrotizing pancreatitis. Octreotide reduces secretion, release and activation of exocrine hormones; there is collection of pancreatic hormones in duct which in return causes irreversible destruction of the exocrine and endocrine pancreatic parenchyma leading to mal-digestion and diabetes. There are lot of controversies in the treatment of acute pancreatitis, so through this study we tried to evaluate whether there is a beneficial role of octreotide or not. Materials and Method: This case control study was done on patients admitted for the treatment of acute pancreatitis at a tertiary care hospital in Central India. This is retrospective study. The data of inpatient records were taken from the medical records department (MRD) of the hospital. The diagnosis of patients was established on basis of biochemical and radiological investigations. The patients were divided into two groups; cases and control, cases had received octreotide along with fluids (group A) controls received fluids without octreotide (group B). Symptomatic treatment was given in both the groups. Ages of the cases and controls were matched (±3 years). The statistical analysis of data was done and results were obtained. Results: In this retrospective case control study the records of fifty two patients were selected. The mean age in Group A was 35 ±16.45 years and in Group B 40±17.51 years in Group B (tA/B1.061; p ˂0.294). There were 22 males and 4 females in group A, while 20 males and 6 females in group B. Both the groups were comparable. All the patients in octreotide group survived while there were three deaths in control group. As far as mean hospital stay is was 10 days ± 7.10 in group A while it was 7 days ±3.65 in group B. All the p values for the criteria of study are non-significant. But when we talk about percentage, 11.53% patient died in control group. Conclusion: In our study we found that octreotide does not affect the final outcome of patients with acute pancreatitis. There is no effect on hospital stay and reduced need of analgesics in patients with acute pancreatitis. Keywords: Acute Pancreatitis; Octreotide; Hospital Stay; Mortality

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Role of mean platelet volume in hypertriglyceridemia-induced acute pancreatitis during pregnancy

10.21203/rs.2.12665/v3 ◽

2020 ◽

Author(s):

Longhuan Zeng ◽

Xueying Cai ◽

Jiayi Chen ◽

Guangyong Jin ◽

Yongke Zheng

Keyword(s):

Acute Pancreatitis ◽

Mean Platelet Volume ◽

Severe Disease ◽

Fetal Mortality ◽

Control Group ◽

Platelet Volume ◽

Pregnant Females ◽

Significant Difference ◽

Relevant Variables

Abstract Background: Hypertriglyceridemia-induced acute pancreatitis during pregnancy (HTG-APP) is a rare but severe disease with high maternal-fetal mortality risk, which constitutes a systemic inflammatory process accompanied by thrombosis and bleeding disorders. However, the role of mean platelet volume (MPV) in HTG-APP remains unclear.Methods: In the retrospective study, we collected 45 patients with HTG-APP as the HTG-APP group and 49 pregnant females with hypertriglyceridemia as the control group. MPV and other relevant variables at onset and remission were collected and compared. Results: MPV were significantly higher in the HTG-APP group than in the control group (P < 0.001), and lower in remission than on onset (P = 0.002). According to the severity of acute pancreatitis, all subjects were classified into mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP) groups. There was a significant difference in MPV on onset among the three groups (P = 0.048), and the SAP patients had the highest levels of MPV. In addition, only in the SAP group, MPV was lower in remission than on onset (P = 0.010). Logistic regression analyses revealed that MPV was significantly associated with SAP (odds ratio = 2.077, 95% confdence interval, 1.038-4.154; P = 0.039). Conclusions: These results may indicate an important role of mean platelet volume in evaluating the severity of HTG-APP.

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