Genetic polymorphisms of manganese-superoxide dismutase and glutathione-S-transferase in chronic alcoholic pancreatitis

Abstract

Chronic alcohol consumption is a major risk factor for the development of chronic pancreatitis. However, chronic pancreatitis occurs only in a minority of heavy drinkers. This variability may be due to yet unidentified genetic factors. Several enzymes involved in the degradation of reactive oxidants and xenobiotics, such as glutathione-S-transferase P1 (GSTP1) and manganese-superoxide dismutase (MnSOD) reveal functional polymorphisms that affect the antioxidative capacity and may therefore modulate the development of chronic pancreatitis and long-term complications like endocrine and exocrine pancreatic insufficiency. Two functional polymorphisms of the MnSOD and the GSTP1 gene were assessed by polymerase chain reaction and restriction fragment length polymorphism in 165 patients with chronic alcoholic pancreatitis, 140 alcoholics without evidence of pancreatic disease and 160 healthy control subjects. The distribution of GSTP1 and MnSOD genotypes were in Hardy-Weinberg equilibrium in the total cohort. Genotype and allele frequencies for both genes were not statistically different between the three groups. Although genotype MnSOD Ala/Val was seemingly associated with the presence of exocrine pancreatic insufficiency, this subgroup was too small and the association statistically underpowered. None of the tested genotypes affected the development of endocrine pancreatic insufficiency. Polymorphisms of MnSOD and GSTP1 are not associated with chronic alcoholic pancreatitis. The present data emphasize the need for stringently designed candidate gene association studies with well-characterized cases and controls and sufficient statistical power to exclude chance observations.

The SOD2 C47T polymorphism influences NAFLD fibrosis severity: Evidence from case-control and intra-familial allele association studies

“…Expression of the SOD2 gene is inducible by a variety of modulators ranging from cytokines to UV irradiation [15] but it is likely that even when induced, the difference between the two allelic variants will be maintained. Our association of T allele carriage with greater NAFLD severity is consistent with the previous small study in a Japanese population [21] and also with studies on other diseases where oxidative stress is likely to be relevant to disease pathogenesis including diabetic nephropathy [22], pancreatic adenocarcinoma [24], exocrine pancreatic insufficiency in chronic alcoholic pancreatitis [39] and diabetic retinopathy [40]. SOD2 is a relatively small gene of 14 kb and consists of a single haplotype block.…”

GSTP1 Ile105Val Polymorphism in Serbian Patients with Pancreatic Diseases

“…The Ile105Val polymorphism alone or in combination with the smoking status was not found to affect the risk of type 2 diabetes mellitus or risk of cardiovascular events in diabetic patients, but it was found to be associated with chronic renal insufficiency (19)(20)(21)(22).…”

Significance of Serum Total Oxidant/Antioxidant Status in Patients with Colorectal Cancer

“…Oxidative stress involves macromolecular oxidative damage, induces tissue protein denaturation, DNA damage, and lipid peroxidation, and interferes with the body's normal metabolic activity, leading to the occurrence and/or development of diseases. It has been confirmed that oxidative stress is involved in a variety of diseases, such as pneumonia[5], pancreatitis[6], diabetic nephropathy[7], cardiovascular disease[8], nervous system disease[9], and cancer[10–13]. Reactive oxygen species (ROS) make up the majority of active oxides, and account for more than 95% of total oxides.…”