BMD values and GSTM3 gene polymorphisms in combination with GSTT1/GSTM1 genes: a genetic association study in Slovenian elderly

Simona Jurkovic Mlakar, Janez Prezelj, Josko Osredkar, Janja Marc
Gerontology 2012, 58 (3): 238-48

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-related products.

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 real-time 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 Val224Ile 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.

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