Common variants in glyoxalase I do not increase chronic pancreatitis risk.
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Glycation End Products, Advanced
/ genetics
Humans
Lactoylglutathione Lyase
/ genetics
Male
Middle Aged
Oxidative Stress
/ genetics
Pancreatitis, Alcoholic
/ genetics
Pancreatitis, Chronic
/ genetics
Polymorphism, Single Nucleotide
/ genetics
Pyruvaldehyde
/ metabolism
Reactive Oxygen Species
/ metabolism
Risk Factors
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
10
06
2019
accepted:
10
09
2019
entrez:
30
10
2019
pubmed:
30
10
2019
medline:
12
3
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31661534
doi: 10.1371/journal.pone.0222927
pii: PONE-D-19-16452
pmc: PMC6818803
doi:
Substances chimiques
Glycation End Products, Advanced
0
Reactive Oxygen Species
0
Pyruvaldehyde
722KLD7415
GLO1 protein, human
EC 4.4.1.5
Lactoylglutathione Lyase
EC 4.4.1.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0222927Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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