title: Antioxidant enzymes GSR, SOD1, SOD2, and CAT gene variants and bone mineral density values in postmenopausal women:  a genetic association analysis.
abstract: OBJECTIVE
  Oxidative stress participates in decreasing bone formation and stimulating bone resorption. Furthermore, antioxidant enzymes have been observed to have low protective activity in women with osteoporosis.The aim of the present study was to examine any association of selected gene polymorphisms of the glutathione S-reductase (GSR), superoxide dismutase (SOD1 and SOD2), and catalase (CAT) genes, alone or in combination, with the bone mineral density (BMD) values of femoral neck (fn), lumbar spine (ls), and total hip (th) in Slovenian postmenopausal women.
  
  
  METHODS
  The gene polymorphisms of CAT, GSR, SOD1, and SOD2 genes in 468 postmenopausal women were analyzed using restriction fragment length polymorphism and a fluorescent 5'-exonuclease genotyping method. BMD_fn, BMD_ls, and BMD_th were measured using dual-energy x-ray absorptiometry. Moreover, univariate statistic analysis and two-way analysis of variance for interaction testing were performed.
  
  
  RESULTS
  A significant association of BMD_th values (P = 0.027) was found in genotype subgroups of 423-287G>A GSR polymorphism located in the third intron among postmenopausal women. Furthermore, women with at least one G allele showed significantly higher levels of BMD_fn (P = 0.044), BMD_th (P = 0.009), and BMD_ls (P = 0.043) than those that are AA homozygotes. Interestingly, the 423-287G>A_GSR*1154-393T>A_GSR combination was significantly associated with BMD_fn (P = 0.013) and BMD_th (P = 0.002) in postmenopausal women.
  
  
  CONCLUSIONS
  The results of our study demonstrate for the first time that antioxidant enzyme GSR gene polymorphisms are significantly associated with BMD, suggesting that the A allele of 423-287G>A GSR polymorphism could contribute to decreased BMD values in postmenopausal women.
authors.affiliation: Clinical Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Simona Jurkovic
authors.initials: SJ
authors.lastname: Mlakar
authors.forename: Josko
authors.initials: J
authors.lastname: Osredkar
authors.forename: Janez
authors.initials: J
authors.lastname: Prezelj
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015519:Bone Density / Q000235:genetics*; D002374:Catalase / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D005260:Female; D005272:Femur Neck; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D005980:Glutathione Reductase / Q000235:genetics*; D006615:Hip; D006801:Humans; D008161:Lumbosacral Region; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics*; D017524:Slovenia; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D002374:Catalase; D005980:Glutathione Reductase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human