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


OBJECTIVE
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).


CONCLUSIONS
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.
Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia. simona.jurkovic@ffa.uni-lj.si
Simona
S
Jurkovic Mlakar
Janez
J
Prezelj
Josko
J
Osredkar
Janja
J
Marc
D000368:Aged; D000375:Aging / Q000235:genetics* / Q000502:physiology; D000704:Analysis of Variance; D015519:Bone Density / Q000235:genetics*; D016723:Bone Remodeling / Q000235:genetics / Q000502:physiology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015577:Geriatric Assessment / Q000379:methods; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010024:Osteoporosis / Q000235:genetics* / Q000503:physiopathology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D017524:Slovenia
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1