Department of Internal Medicine I, Martin Luther University, Halle, Germany.
Medical Department II-Gastroenterology, Hepatology, Infectious Diseases, Pulmonology, University of Leipzig Medical Center, Leipzig, Germany.
PLoS One. 2019 Oct 29;14(10):e0222927. doi: 10.1371/journal.pone.0222927. eCollection 2019.
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.
慢性胰腺炎（CP）可能由氧化应激引起。活性氧（ROS）的一个重要来源是甲基乙二醛衍生的高级糖基化终产物（AGE）的形成。甲基乙二醛通过 Glyoxalase I（GLO1）解毒。GLO1 活性的降低会导致 ROS 增加。GLO1 的单核苷酸多态性（SNP）与各种炎症性疾病有关。在这里，我们分析了常见的 GLO1 变体是否与酒精性（ACP）和非酒精性 CP（NACP）相关。
使用熔解曲线分析，我们对 223 名 ACP、218 名 NACP 患者和 328 名对照者进行了 11 个由 SNPinfo LD TAG SNP 选择工具和功能相关变体 rs4746 定义的标记 SNP 的基因分型。对于选定的变体，将队列扩展到多达 1441 个患者样本。
在 ACP 队列中，与 rs1937780 的基因型相比，患者与对照组之间的比较在筛查队列中显示出不确定的结果（p = 0.08）。然而，在 1441 名患者的扩展队列中，基因型比较没有发现统计学显著的相关性（p = 0.11），逻辑回归分析也没有发现相关性（p = 0.214，OR 1.072，95%CI 0.961-1.196）。在 NACP 筛查队列中，当患者与对照组进行隐性或显性模型比较时，SNP rs937662、rs1699012 和 rs4746 显示出不确定的结果（p = 0.08、0.08 和 0.07）。同样，这些关联在扩展队列中也没有得到证实（rs937662，显性模型：p = 0.07，逻辑回归：p = 0.07，OR 1.207，95%CI 0.985-1.480）或在 rs4746 的复制队列中（德国，p = 0.42，OR 1.080，95%CI 0.673-1.124；法国，p = 0.19，OR 0.90，95%CI 0.76-1.06；中国，p = 0.24，OR 1.18，95%CI 0.90-1.54）和 rs1699012（德国，慕尼黑；p = 0.279，OR 0.903，95%CI 0.750-1.087）。
常见的 GLO1 变体不会增加慢性胰腺炎的风险。
