Dataset Information

Increased risk of acute pancreatitis occurrence in smokers with rs5751901 polymorphisms in GGT1 gene.

ABSTRACT: Objectives: The study was aimed to assess ??glutamyltransferase (GGT) activity and concentration as a marker of oxidative stress induced by exposure to tobacco smoke in acute pancreatitis (AP) course. Examination of the relationship between GGT activity/concentration and single-nucleotide polymorphism (SNP rs5751901 and rs2236626) in GGT1 gene was performed. Subjects and methods: We examined SNPs in 38 AP patients and 51 healthy subjects by PCR-RFLP methods. GGT concentration in blood was measured with the use of the ELISA method; GGT activity and GSH concentration were measured by the Szasz and Patterson methods, respectively. Results: In the non-AP smokers group with TC genotype for SNPrs5751901 an increased blood GGT activity compared to smokers with CC genotypes was shown. In the course of AP was observed an elevated GGT activity and the value of GGT activity/GGT concentration ratio in smokers compared to non-smokers, in AP patients with TC genotypes and CC genotypes, respectively, for both SNP: rs5751901 and rs2236626. In the group of smoking AP patients with the CC and TC genotypes in rs5751901 locus and CC and TT genotypes in rs2236626 locus a decreases in GSH concentration during hospitalization were noted. Conclusions: SNP rs5751901 and rs2236626 cause changes in GGT activity. Smoking in the AP course contributes to increased GGT activity and excessive GSH use up in patients with TC and CC genotypes for both SNPs. Exposure to smoke xenobiotics enhances (3-fold) the risk of AP occurrence in individuals with TC genotypes for SNP rs5751901.

SUBMITTER: Sciskalska M

PROVIDER: S-EPMC6990886 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Increased risk of acute pancreatitis occurrence in smokers with rs5751901 polymorphisms in GGT1 gene.

Ściskalska Milena M Ołdakowska Monika M Marek Grzegorz G Milnerowicz Halina H

International journal of medical sciences 20200114 2

<b>Objectives</b>: The study was aimed to assess γ‑glutamyltransferase (GGT) activity and concentration as a marker of oxidative stress induced by exposure to tobacco smoke in acute pancreatitis (AP) course. Examination of the relationship between GGT activity/concentration and single-nucleotide polymorphism (SNP rs5751901 and rs2236626) in GGT1 gene was performed. <b>Subjects and methods</b>: We examined SNPs in 38 AP patients and 51 healthy subjects by PCR-RFLP methods. GGT concentration in bl ...[more]

PMID: 32038108

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Project description:IntroductionLung cancer is the predominant cause of death among cancer patients and non-small cell lung cancer (NSCLC) is the most common type. Cigarette smoking is the prevailing risk factor for NSCLC, nevertheless, this cancer is also diagnosed in never-smokers. B and T lymphocyte attenuator (BTLA) belongs to immunological checkpoints which are key regulatory molecules of the immune response. A growing body of evidence highlights the important role of BTLA in cancer. In our previous studies, we showed a significant association between BTLA gene variants and susceptibility to chronic lymphoblastic leukemia and renal cell carcinoma in the Polish population. The present study aimed to analyze the impact of BTLA polymorphic variants on the susceptibility to NSCLC and NSCLC patients' overall survival (OS).MethodsUsing TaqMan probes we genotyped seven BTLA single-nucleotide polymorphisms (SNPs): rs2705511, rs1982809, rs9288952, rs9288953, rs1844089, rs11921669 and rs2633582 with the use of ViiA 7 Real-Time PCR System.ResultsWe found that rs1982809 within BTLA is associated with NSCLC risk, where carriers of rs1982809G allele (AG+GG genotypes) were more frequent in patients compared to controls. In subgroup analyses, we also noticed that rs1982809G carriers are significantly overrepresented in never-smokers, but not in smokers compared to controls. Additionally, the global distribution of the haplotypes differed between the never-smokers and smokers, where haplotypes A G G C A, C G A C G, and C G A T G were more frequent in never-smoking patients. Furthermore, the presence rs1982809G (AG+GG genotypes) allele as well as the presence of rs9288953T allele (CT+TT genotypes) increased NSCLC risk in females' patients. After stratification by histological type, we noticed that rs1982809G and rs2705511C carriers were more frequent among adenocarcinoma patients. Moreover, rs1982809G and rs2705511C correlated with the more advanced stages of NSCLC (stage II and III), but not with stage IV. Furthermore, we showed that rs2705511 and rs1982809 significantly modified OS, while rs9288952 tend to be associated with patients' survival.ConclusionOur results indicate that BTLA polymorphic variants may be considered low penetrating risk factors for NSCLC especially in never-smokers, and in females, and are associated with OS of NSCLC patients.

Project description:BackgroundMost patients with acute pancreatitis (AP) experience mild, self-limiting disease with little or no need for hospital care. However, 20-25% of patients develop a more severe and potentially life-threatening condition with progressive systemic inflammatory response syndrome (SIRS) and multiorgan failure, resulting in high morbidity and mortality rates. Predicting disease severity at an early stage is important, as immediate supportive care has been demonstrated to reduce the incidence of SIRS and organ failure, improving patient outcome. Several studies have demonstrated elevated levels of heparin-binding protein (HBP) in patients with sepsis and septic shock, and HBP is believed to play a part in endothelial dysfunction leading to vascular leakage. As HBP levels increase prior to other known biomarkers, HBP has emerged as a promising early predictor of severe sepsis with organ dysfunction.MethodsPatients admitted to Skåne University Hospital in Malmö between 2010 and 2013 fulfilling the criteria for AP were identified in the emergency department and prospectively enrolled in this study. The primary outcome was measured levels of HBP upon hospital admission in patients with confirmed AP. Correlations among HBP concentrations, disease severity and fluid balance were considered secondary endpoints. The correlation between HBP levels and fluid balance were analysed using Pearson correlation, and the ability of HBP to predict moderately severe/severe AP was assessed using a receiver operating characteristic (ROC) curve.ResultsThe overall median HBP level in this study was 529 (307-898) ng/ml. There were no significant group differences in HBP levels based on AP severity. Fluid balance differed significantly between patients with mild versus moderately severe and severe pancreatitis, but we found no correlation between HBP concentration and fluid balance.ConclusionsHBP levels are dramatically increased in patients with AP, and these levels far exceed those previously reported in other conditions. In this study, we did not observe any significant correlation between HBP levels and disease severity or the need for intravenous fluid. Additional studies on HBP are needed to further explore the role of HBP in the pathogenesis of AP and its possible clinical implications.

Dataset Information

Increased risk of acute pancreatitis occurrence in smokers with rs5751901 polymorphisms in GGT1 gene.

Publications

Increased risk of acute pancreatitis occurrence in smokers with rs5751901 polymorphisms in GGT1 gene.

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