BMD values and GSTM3 gene polymorphisms in combination with GSTT1/GSTM1 genes: a genetic association study in Slovenian elderly : Simona Jurkovic Mlakar ... [et al.]
Jurković Mlakar, Simona (Author), Preželj, Janez (Author), Osredkar, Joško (Author), Marc, Janja (Author)

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Background: Much research suggests that oxidative stress is associated with osteoporosis development. Glutathione S-transferases mu3 (GSTM3) are an important group of detoxifying enzymes that eliminate oxidative stress-relatedproducts. Objectives: To examine the associations of functional GSTM3 gene polymorphisms (Val224Ile and insdelAGG), their haplotypes and, in combination with GSTT1- null and GSTM1-null polymorphisms, with bone mineral density (BMD) measured at femoral neck (_fn), lumbar spine (_ls) and total hip(_th) and biochemical bone turnover markers in 593 Slovenian elderly women and 119 Slovenian elderly men. Methods: GSTM3, GSTT1-null and GSTM1-null gene polymorphisms using sizing denaturing high-performance liquid chromatography, triplex PCR method or realtime PCR; BMD_fn, BMD_ls, BMD_th values using dual energy X-ray absorptiometry, and plasma osteocalcin, serum bone alkaline phosphatase and free soluble tumor necrosis factor (ligand) superfamily, member 11 (sRANKL) concentrations using a solid-phase, two-site chemiluminescent enzyme- labeled immunometric assay, radioimmunoassay or enzyme immunoassay were determined. Statistical analysis was performed using one-way and two-way ANCOVA with adjustment for potential confounders (age, height and weight). Results: The (borderline) significant differences in BMD_th and BMD_fn values between genotype subgroups of Val224Ile polymorphism of GSTM3 gene (p = 0.057 and 0.053, respectively) with the lowest BMD values among heterozygotes and between 224Ile-insAGG haplotype subgroups (p = 0.048 and 0.019, respectively) were found. Significant differences of BMD_fn between the 224Ile-delAGG haplotype subgroups were observed (p = 0.012). Association of 224Val-insAGG with BMD_fn was of borderline significance (p = 0.062). Conclusion: The results of our study demonstrate the genetic association between detoxifying enzyme GSTM3 and BMD variation, suggesting that the Val- 224Ile polymorphism and 224Ile-insAGG haplotype could be used for further evaluation of the impact of GSTs gene polymorphisms on osteoporosis, using larger cohorts in searching for osteoporosis risk markers.

Keywords:osteoporoza, oksidativni stres, osteoporotični genski markerji, HPLC
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Number of pages:str. 238-248
Numbering:Vol. 58, no. 3
ISSN on article:0304-324X
DOI:10.1159/000335048 Link is opened in a new window
COBISS.SI-ID:3198833 Link is opened in a new window
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Shortened title:Gerontology
Publisher:S. Karger
COBISS.SI-ID:25525760 This link opens in a new window

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