title: GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case-control study.
abstract: OBJECTIVE
  Oxidative stress is recognized as an important factor in progressive myoclonus epilepsy (PME). Genetic polymorphism of glutathione S-transferases (GSTs), which are involved in both protection from oxidative damage and detoxification, might alter the capacity for protecting tissues from exogenous and endogenous oxidants. We aimed to assess a possible association between GST polymorphism and PME, as well as, correlation between GST genotypes and oxidative phenotype in PME patients.
  
  
  METHODS
  GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 26 patients with PME and 66 controls. Byproducts of protein oxidative damage (thiol groups (P-SH) and nitrotyrosine), superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were determined.
  
  
  RESULTS
  The frequency of GSTA1, GSTM1 and GSTP1 genotypes was not significantly different between PME patients and controls, while individuals with GSTT1-null genotype were at 5.44-fold higher risk of PME than carriers of GSTT1-active genotype. Moreover, significant risk of PME was obtained in carriers of both GSTT1-null and GSTM1-null genotypes. Carriers of combined GSTA1- active and GSTT1-null genotype were at highest, 7.55-fold increased risk of PME. Byproducts of protein damage did not reach statistical significance, while SOD and GPX activities were significantly higher in PME patients then in controls. When stratified according to GST genotype, P-SH groups were significantly lower only in patients with GSTT1-null genotype in comparison to carriers of active genotype. Only SOD activity was increased in GSTT1-null when compared to corresponding active genotype.
  
  
  CONCLUSIONS
  GSTT1-null genotype might be associated with the increased risk and enhanced susceptibility to oxidative stress in PME patients.
authors.affiliation: Clinic of Neurology, Clinical Centre of Serbia, Dr Subotica 2, 11000 Belgrade, Serbia; Faculty of Medicine, University in Belgrade, Belgrade, Serbia. Electronic address: ercegovacmarko@gmail.com.
authors.forename: Marko
authors.initials: M
authors.lastname: Ercegovac
authors.affiliation: Clinic of Neurology and Psychiatry for Children and Youth, Clinical Centre of Serbia, Dr Subotica 6a, 11000 Belgrade, Serbia; Faculty of Medicine, University in Belgrade, Belgrade, Serbia. Electronic address: njjovic@eunet.rs.
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Jovic
authors.affiliation: Clinic of Neurology, Clinical Centre of Serbia, Dr Subotica 2, 11000 Belgrade, Serbia; Faculty of Medicine, University in Belgrade, Belgrade, Serbia. Electronic address: dragoslav.sokic@kcs.ac.rs.
authors.forename: Dragoslav
authors.initials: D
authors.lastname: Sokic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Pasterova 2, 11000 Belgrade, Serbia; Faculty of Medicine, University in Belgrade, Belgrade, Serbia. Electronic address: anasavicradojevic@med.bg.ac.rs.
authors.forename: Ana
authors.initials: A
authors.lastname: Savic-Radojevic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Pasterova 2, 11000 Belgrade, Serbia; Faculty of Medicine, University in Belgrade, Belgrade, Serbia. Electronic address: coricmvesna@gmail.com.
authors.forename: Vesna
authors.initials: V
authors.lastname: Coric
authors.affiliation: Institute of Medical and Clinical Biochemistry, Pasterova 2, 11000 Belgrade, Serbia. Electronic address: tanjajevtic@gmail.com.
authors.forename: Tanja
authors.initials: T
authors.lastname: Radic
authors.affiliation: University Children's Hospital, Tirsova 10, 11000 Belgrade, Serbia; Faculty of Medicine, University in Belgrade, Belgrade, Serbia. Electronic address: dimitrije.nikolic@gmail.com.
authors.forename: Dimitrije
authors.initials: D
authors.lastname: Nikolic
authors.affiliation: Faculty of Biology, University in Belgrade, Studentski trg 3, 11000 Belgrade, Serbia. Electronic address: miljana@bio.bg.ac.rs.
authors.forename: Miljana
authors.initials: M
authors.lastname: Kecmanovic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Pasterova 2, 11000 Belgrade, Serbia; Faculty of Medicine, University in Belgrade, Belgrade, Serbia. Electronic address: marija_opacic@yahoo.com.
authors.forename: Marija
authors.initials: M
authors.lastname: Matic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Pasterova 2, 11000 Belgrade, Serbia; Faculty of Medicine, University in Belgrade, Belgrade, Serbia. Electronic address: tatjanasimic@med.bg.ac.rs.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Simic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Pasterova 2, 11000 Belgrade, Serbia; Faculty of Medicine, University in Belgrade, Belgrade, Serbia. Electronic address: marijaercegovac@med.bg.ac.rs.
authors.forename: Marija
authors.initials: M
authors.lastname: Pljesa-Ercegovac
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D020191:Myoclonic Epilepsies, Progressive / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D015415:Biomarkers; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C484555:GSTA1 protein, human; C496556:GSTP1 protein, human
keywords: Glutathione S-transferases; Oxidative stress; Progressive myoclonus epilepsy; Risk