Alcohol & Alcoholism Vol. 39, No. 6 © Medical Council on Alcohol 2004; all rights reserved
THE ROLE OF POLYMORPHISMS OF GLUTATHIONE S-TRANSFERASES GSTM1, M3, P1, T1 AND A1 IN SUSCEPTIBILITY TO ALCOHOLIC LIVER DISEASE
1 Department of Gastroenterology, 2 Human Genomics Research Group, Institute for Science and Technology in Medicine, Keele University School of Medicine, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire, 3 Department of Pharmacology and Therapeutics, The University of Liverpool, Ashton Street, 4 Gastroenterology Unit, The Royal Liverpool and Broadgreen University Hospital Trust, Prescot Street, Liverpool and 5 Department of Gastroenterology, Dudley Group of Hospitals, Dudley, UK
* Author to whom correspondence should be addressed at: Department of Gastroenterology, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire UK ST4 6QG. E-mail: alison.brind{at}uhns.nhs.uk
(Received 13 July 2004; first review notified 28 August 2004; in revised form 29 September 2004; accepted 1 October 2004)
Aims and Methods: Oxidant stress is proposed to be an important pathogenic factor in liver damage related to alcohol. The glutathione S-transferases (GSTs) are a group of polymorphic enzymes that are important in protection against oxidant stress. As there is evidence for genetic susceptibility to alcohol-related liver disease we have compared the frequency of polymorphisms of GSTM1, M3, P1, T1 and A1 by polymerase chain reaction (PCR) on leucocyte DNA in patients from North Staffordshire, Birmingham and Liverpool with alcohol-related chronic liver disease heavy drinking and normal local controls. Results: There were no significant differences in GSTM1, GSTM3 or GSTP1 genotype frequencies among patients, drinking and non-drinking controls from the three centres. There was a significant increase in the GSTT1 null Liverpool alcoholic liver disease (ALD) patients compared with corresponding non-drinking controls (26.3 and 14.6%, respectively; P = 0.044, odds ratio (OR) = 2.1, 95% CI = 1.1–4.7) though this was not repeated in the Birmingham and North Staffordshire cohorts. For GSTA1, the –69 CC genotype was associated with increased risk of ALD in the Liverpool group, but a reduced risk in the North Staffordshire group. Conclusions: We have failed to demonstrate within the limitation of a case–control study a reproducible significant association of GST polymorphisms with susceptibility to ALD but there are suggestions that GSTA1 and GSTT1 warrant further study.
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