title: Copy number variation in glutathione S-transferases M1 and T1 and ischemic vascular disease: four studies and meta-analyses.
abstract: BACKGROUND
  Glutathione S-transferases (GSTs) M1 and T1 detoxify products of oxidative stress and may protect against atherosclerosis and ischemic vascular disease (IVD). We tested the hypothesis that copy number variation (CNV) in GSTM1 and GSTT1 genes, known to be associated with stepwise decreases in catalytic activity, predict risk of IVD.
  
  
  RESULTS
  We included 23 059 Danes from 2 general population studies and 2 case-control studies, of whom 4930 had ischemic heart disease (IHD) and 2086 had ischemic cerebrovascular disease. A real-time polymerase chain reaction method genotyped for the exact number of GSTM1 and GSTT1 gene copies. We also performed meta-analyses, including our own and former studies, totaling 13 196 IHD cases and 33 228 controls. CNV in GSTM1 or GSTT1 or genotype combinations were not associated with an increased risk of IHD, myocardial infarction, ischemic cerebrovascular disease, ischemic stroke, or any ischemic vascular event in studies individually or combined or in the meta-analyses. Furthermore, genotypes did not interact with smoking on risk of disease end points. Finally, GST genotypes did not associate with markers of inflammation and oxidation or interact with smoking on markers of inflammation in the general population. In contrast, we observed the well-established association between CNV in GSTM1 and risk of bladder cancer.
  
  
  CONCLUSIONS
  In studies including 6557 IVD cases and 16 502 controls and in meta-analyses of 13 196 cases and 33 228 controls, CNV in GSTM1 and GSTT1 genes did not associate with risk of IVD or with markers of inflammation. These observations were independent of smoking exposure.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Marianne S
authors.initials: MS
authors.lastname: Nørskov
authors.forename: Ruth
authors.initials: R
authors.lastname: Frikke-Schmidt
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.forename: Henrik
authors.initials: H
authors.lastname: Sillesen
authors.forename: Peer
authors.initials: P
authors.lastname: Grande
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjaerg-Hansen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D002545:Brain Ischemia; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007249:Inflammation; D007511:Ischemia; D008297:Male; D008875:Middle Aged; D012907:Smoking; D014652:Vascular Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology
chemical_list: D015415:Biomarkers; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1