Journal Article

Common variants in glyoxalase I do not increase chronic pancreatitis risk

Zuppardo, Raffaella Alessia, Férec, Claude, te Morsche, Rene H. M., Hollenbach, Marcus, Hegyi, Peter, Ruffert, Claudia, Głuszek, Stanislaw, Kirsten, Holger, Keil, Bettina, Liao, Zhuan, Kaune, Tom, Drenth, Joost PH, Witt, Heiko, Michl, Patrick, Cavestro, Giulia Martina, Masson, Emmanuelle, Weiss, Frank Ulrich, Scholz, Markus, Tóth, Andrea, Rosendahl, Jonas, Griesmann, Heidi, Chen, Jian-Min, Becker, Carla, Malecka-Panas, Ewa, Grützmann, Robert, Zou, Wen-Bin, Riedel, Jan, Saftoiu, Adrian, Lerch, Markus M., Ewers, Maren, Hoffmeister, Albrecht, Bugert, Peter, Damm, Marko

2019

Overview

Chronic pancreatitis (CP) may be caused by oxidative stress. An important source of reactive oxygen species (ROS) is the methylglyoxal-derived formation of advanced glycation endproducts (AGE). Methylglyoxal is detoxified by Glyoxalase I (GLO1). A reduction in GLO1 activity results in increased ROS. Single nucleotide polymorphisms (SNPs) of GLO1 have been linked to various inflammatory diseases. Here, we analyzed whether common GLO1 variants are associated with alcoholic (ACP) and non-alcoholic CP (NACP). Using melting curve analysis, we genotyped a screening cohort of 223 ACP, 218 NACP patients, and 328 controls for 11 tagging SNPs defined by the SNPinfo LD TAG SNP Selection tool and the functionally relevant variant rs4746. For selected variants the cohorts were extended to up to 1,441 patient samples. In the ACP cohort, comparison of genotypes for rs1937780 between patients and controls displayed an ambiguous result in the screening cohort (p = 0.08). However, in the extended cohort of 1,441 patients no statistically significant association was found for the comparison of genotypes (p = 0.11), nor in logistic regression analysis (p = 0.214, OR 1.072, 95% CI 0.961-1.196). In the NACP screening cohort SNPs rs937662, rs1699012, and rs4746 displayed an ambiguous result when patients were compared to controls in the recessive or dominant model (p = 0.08, 0.08, and 0.07, respectively). Again, these associations were not confirmed in the extended cohorts (rs937662, dominant model: p = 0.07, logistic regression: p = 0.07, OR 1.207, 95% CI 0.985-1.480) or in the replication cohorts for rs4746 (Germany, p = 0.42, OR 1.080, 95% CI 0.673-1.124; France, p = 0.19, OR 0.90, 95% CI 0.76-1.06; China, p = 0.24, OR 1.18, 95% CI 0.90-1.54) and rs1699012 (Germany, Munich; p = 0.279, OR 0.903, 95% CI 0.750-1.087). Common GLO1 variants do not increase chronic pancreatitis risk.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Advanced glycosylation end products / Aging (Biology) / Biology and Life Sciences / Cancer / Chromosomes / Development and progression / Endoscopy / Epidemiology / Female / Fibrosis / Gastroenterology / Genetic Association Studies / Genetic polymorphisms / Genetic Predisposition to Disease / Genotype / Genotypes / Glycation End Products, Advanced - genetics / Glycosylation / Health aspects / Health informatics / Hepatology / Humans / Infectious diseases / Inflammatory diseases / Internal medicine / Lactoylglutathione lyase / Lactoylglutathione Lyase - genetics / Male / Medicine / Medicine and Health Sciences / Melting curve / Middle Aged / Nucleotides / Oxidative stress / Oxidative Stress - genetics / Oxygen / Pancreatitis / Pancreatitis, Alcoholic - genetics / Pancreatitis, Alcoholic - metabolism / Pancreatitis, Alcoholic - pathology / Pancreatitis, Chronic - genetics / Pancreatitis, Chronic - metabolism / Pancreatitis, Chronic - pathology / People and Places / Physical Sciences / Polymorphism, Single Nucleotide - genetics / Pyruvaldehyde / Pyruvaldehyde - metabolism / Reactive oxygen species / Reactive Oxygen Species - metabolism / Regression analysis / Research and Analysis Methods / Risk Factors / Screening / Single nucleotide polymorphisms / Single-nucleotide polymorphism / Social Sciences / Statistical analysis / Statistical methods / Tagging