TY - JOUR
T1 - Common variants in glyoxalase I do not inease chronic pancreatitis risk
AU - Kaune, Tom
AU - Hollenbach, Marcus
AU - Keil, Bettina
AU - Chen, Jian-Min
AU - Masson, Emmanuelle
AU - Becker, Carla
AU - Damm, Marko
AU - Ruffert, Claudia
AU - Grützmann, Robert
AU - Hoffmeister, Albrecht
AU - te Morsche, Rene H. M.
AU - Cavestro, Giulia Martina
AU - Zuppardo, Raffaella Alessia
AU - Saftoiu, Adrian
AU - Malecka-Panas, Ewa
AU - Głuszek, Stanislaw
AU - Bugert, Peter
AU - Lerch, Markus M.
AU - Weiss, Frank Ulrich
AU - Zou, Wen-Bin
AU - Liao, Zhuan
AU - Hegyi, Peter
AU - Drenth, Joost P. H.
AU - Riedel, Jan
AU - Férec, Claude
AU - Scholz, Markus
AU - Kirsten, Holger
AU - Tóth, Andrea
AU - Ewers, Maren
AU - Witt, Heiko
AU - Griesmann, Heidi
AU - Michl, Patrick
AU - Rosendahl, Jonas
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Introduction 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). Methods 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. Results 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). Conclusions Common GLO1 variants do not increase chronic pancreatitis risk.
AB - Introduction 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). Methods 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. Results 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). Conclusions Common GLO1 variants do not increase chronic pancreatitis risk.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074280588&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31661534
U2 - https://doi.org/10.1371/journal.pone.0222927
DO - https://doi.org/10.1371/journal.pone.0222927
M3 - Article
C2 - 31661534
SN - 1932-6203
VL - 14
JO - PLOS ONE
JF - PLOS ONE
IS - 10
M1 - e0222927
ER -