Schneider Alexander, Rosendahl Jonas, Bugert Peter, Weiss Christel, Unterschütz Heike, Kylanpää-Bäck Marja-Leena, Lempinen Marko, Kemppainen Esko, Diaconu Brindusa L, Ebert Matthias P, Pfützer Roland H
Department of Medicine II, University Medical Centre Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany.
University Clinic and Policlinic of Internal Medicine I, University Clinic of Halle, Ernst-Grube-Straße 40, 06120 Halle (Saale), Germany.
Alcohol Alcohol. 2017 Sep 1;52(5):535-541. doi: 10.1093/alcalc/agx039.
Oxidative stress may contribute to the development of chronic pancreatitis (CP). The enzymes manganese superoxide dismutase 2 (MnSOD, SOD2) and catalase (CAT) counteract free radical activity within the mitochondria and the cytosol. Moreover, CAT activity contributes to the transformation of ethanol to acetaldehyde, a toxic intermediate product of ethanol metabolism, which has been associated with pancreatic damage. Common functional polymorphisms have been described in the MnSOD gene [rs4880, NM_000636.3:c.47 T > C, alanine (ALA) to valine (Val)] and in the CAT promoter region [rs1001179, NG_013339.1:g.4760 C > T]. We investigated whether these polymorphisms are associated with alcoholic CP.
We genotyped 470 patients with alcoholic CP for these MnSOD and CAT polymorphisms. We also analysed these variants in 357 healthy control subjects, and in an additional control group of 113 individuals with non-alcoholic CP. We used the age at onset of CP as marker of disease severity and investigated whether different genotypes are associated with different ages at onset. In patients with alcoholic CP, we investigated whether an interaction exists between smoking behaviour and genotypes by comparing genotype distributions in smokers and non-smokers.
We did not observe significant differences of genotype frequencies between patient groups and controls. In patient groups, we did not find significant differences in the ages at onset between different genotypes. We did not observe an interaction between these polymorphisms. We did not find an association of these variants with smoking behaviour.
The investigated MnSOD and CAT polymorphisms do not predispose to the development of alcoholic CP.
Patients with alcoholic pancreatitis and controls were genotyped for polymorphisms in oxidative stress genes. There were no significant differences of genotype frequencies between patients and controls, and no association with the age at onset of disease was observed. The polymorphisms are not associated with the development of alcoholic pancreatitis.
氧化应激可能促使慢性胰腺炎(CP)的发生。锰超氧化物歧化酶2(MnSOD,SOD2)和过氧化氢酶(CAT)可抵消线粒体和细胞质内的自由基活性。此外,CAT活性有助于将乙醇转化为乙醛,乙醛是乙醇代谢的一种有毒中间产物,与胰腺损伤有关。MnSOD基因[rs4880,NM_000636.3:c.47 T>C,丙氨酸(ALA)变为缬氨酸(Val)]和CAT启动子区域[rs1001179,NG_013339.1:g.4760 C>T]中已发现常见的功能多态性。我们研究了这些多态性是否与酒精性CP相关。
我们对470例酒精性CP患者进行了这些MnSOD和CAT多态性的基因分型。我们还在357名健康对照者以及另外113名非酒精性CP个体的对照组中分析了这些变异。我们将CP发病年龄作为疾病严重程度的指标,并研究不同基因型是否与不同发病年龄相关。在酒精性CP患者中,我们通过比较吸烟者和非吸烟者的基因型分布,研究吸烟行为与基因型之间是否存在相互作用。
我们未观察到患者组与对照组之间基因型频率的显著差异。在患者组中,我们未发现不同基因型之间发病年龄的显著差异。我们未观察到这些多态性之间存在相互作用。我们未发现这些变异与吸烟行为有关联。
所研究的MnSOD和CAT多态性不会使个体易患酒精性CP。
对酒精性胰腺炎患者和对照者进行了氧化应激基因多态性的基因分型。患者与对照者之间基因型频率无显著差异,且未观察到与疾病发病年龄的关联。这些多态性与酒精性胰腺炎的发生无关。