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Antioxidant enzymes GSR, SOD1, SOD2, and CAT gene variants and bone mineral density values in postmenopausal women: a genetic association analysis

Mlakar, Simona Jurkovic PhD1; Osredkar, Josko PhD1; Prezelj, Janez PhD2; Marc, Janja PhD3

Menopause: The Journal of The North American Menopause Society: March 2012 - Volume 19 - Issue 3 - p 368–376
doi: 10.1097/gme.0b013e31822d5b10
Original Articles
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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.

The results of this study demonstrate for the first time that antioxidant enzyme glutathione S-reductase (GSR) gene polymorphisms are significantly associated with bone mineral density, suggesting that the A allele of 423-287G>A GSR polymorphism could contribute to decreased bone mineral density values in postmenopausal women.

From the 1Clinical Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Ljubljana, Slovenia; 2Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia; and 3Faculty of Pharmacy,Department of Clinical Biochemistry, University of Ljubljana, Ljubljana,Slovenia.

Received May 16, 2011; revised and accepted July 12, 2011.

Funding/support: The study was supported by a PhD scholarship, research program P3-0298, and project L3-2330 at the Research Agency of Slovenia.

Financial disclosure/conflicts of interest: None reported.

All authors have full control of all primary data and agree to allow the journal to review their data if requested.

Ethical standards: All authors declare that the experiments comply with the current laws of the Republic of Slovenia.

Address correspondence to: Janja Marc, MPharm, PhD, Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, SI-1000 Ljubljana, Slovenia. E-mail: janja.marc@ffa.uni-lj.si

©2012The North American Menopause Society