Effect of glutathione S-transferase M1 genotype on progression of atherosclerosis in lifelong male smokers
Introduction
Differences in genotype for enzyme systems involved in the biotransformation from cigarette smoke metabolites may differentiate the risk for cardiovascular disease among smokers [1]. The glutathione S-transferase μ1 (GSTM1) polymorphism is particularly relevant, as 50% of the general Caucasian population lacks GSTM1 enzyme activity due to two deficient GSTM1 null allelles (GSTM1-0) [2]. The enzyme GSTM1 is a member of a family of transferase enzymes. These enzymes are involved in detoxifying potential atherogenic substances such as reactive oxygen species and tobacco smoke carcinogens, including the polycyclic aromatic hydrocarbons from cigarette tar, by conjugating them to glutathion [3], [4]. Several glutathione transferases can participate in metabolism of cytotoxic aldehydes produced during lipid peroxidation, such as 4-hydroxynonenal. The transferases accelerate the reactions of these aldehydes with GSH to give less toxic conjugates [5].
We hypothesize that smokers with the GSTM1-0 genotype have increased progression of atherosclerosis. This was studied among 189 male lifelong smokers who had participated in a double-blind placebo-controlled intervention trial on the effect of 400 IU vitamin E supplementation on 2-year change of the common carotid intima media thickness (CCA-IMT). CCA-IMT change was measured by B-mode ultrasound as a valid and highly reproducible marker for atherosclerosis [6], [7], [8].
Section snippets
Methods
The present study utilized data derived from a double-blind placebo controlled 2-year intervention trial among male lifelong smokers on the effect of 400 IU vitamin E on the 2-year change in the common carotid intima media thickness (CCA-IMT).
For this intervention male inhabitants born between 1919 and 1946 from Nijmegen, a city in the Netherlands, were approached using addresses obtained from the Municipal Registration Office. The recruitment period was from October 1995 to July 1996. Eligible
Results
Baseline values for CCA-IMT were higher in the group with the GSTM1 null-compared to the positive genotype (borderline significant, P=0.09) (Table 1). At baseline no significant differences were observed in age, body mass index, smoking characteristics, plasma lipids, CVD history and hypertension between the GSTM1-1 and GSTM1-0 group (Table 1). Remarkable is the non-significant higher prevalence of CVD history and the significant higher CVD medication use in the smokers with the GSTM1-0
Discussion
In this study the 2-year progression of common carotid intima media thickness (CCA-IMT) was clearly more increased for smokers with the GSTM1-0 genotype, thus lacking the detoxification enzyme glutathione S-transferase μ, compared to smokers with the GSTM1-1 genotype. Although not statistically significant, vitamin E supplementation in smokers with the GSTM1-0 type may be beneficial shown by 46% lower increase in progression of CCA-IMT.
Studies are available on GSTM1 genotype showing increased
Acknowledgements
This study was financially supported by Research Grant #94.106 of the Netherlands Heart Foundation. Vitamin analysis as well as vitamin E and placebo capsules were provided by F Hoffman La Roche Ltd., Basel. We would like to acknowledge the following persons for assistance in collecting the data and for assistance in ultrasound measurements: T. Terburg, F.H.M.W. van Rooij, H. Van Langen, M. Brok, and A. Theloose.
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