Mutagenesis Advance Access originally published online on June 4, 2007
Mutagenesis 2007 22(5):305-310; doi:10.1093/mutage/gem017
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Genetic polymorphisms of manganese-superoxide dismutase and glutathione-S-transferase in chronic alcoholic pancreatitis
1Department of Medicine, Columbia University, NY, USA 2Interdisciplinary Center of Clinical Research, University of Erlangen-Nuremberg, Erlangen, Germany 3Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany 4Department of Medicine I, University of Lübeck, Lübeck, Germany 5Department of Medicine I, University of Regensburg, Regensburg, Germany 6Department of General Surgery, University of Heidelberg, Heidelberg, Germany 7Department of Medicine, Salem Medical Center, University of Heidelberg, Heidelberg, Germany 8Institute of Clinical Pharmacology, University of Berne, Switzerland
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.
* To whom correspondence should be addressed. Tel: +49 31 632 8715; Fax: +49 31 632 4997; Email: felix.stickel{at}ikp.unibe.ch
Received on February 19, 2007; revised on March 30, 2007; accepted on April 3, 2007.