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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 (Avtor), Preželj, Janez (Avtor), Osredkar, Joško (Avtor), Marc, Janja (Avtor)

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Izvleček
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.

Jezik:Angleški jezik
Ključne besede:osteoporoza, oksidativni stres, osteoporotični genski markerji, HPLC
Vrsta gradiva:Delo ni kategorizirano (r6)
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:FFA - Fakulteta za farmacijo
Leto izida:2012
Št. strani:str. 238-248
Številčenje:Vol. 58, no. 3
UDK:577
ISSN pri članku:0304-324X
DOI:10.1159/000335048 Povezava se odpre v novem oknu
COBISS.SI-ID:3198833 Povezava se odpre v novem oknu
Število ogledov:654
Število prenosov:168
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
 
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Naslov:Gerontology
Skrajšan naslov:Gerontology
Založnik:S. Karger
ISSN:0304-324X
COBISS.SI-ID:25525760 Povezava se odpre v novem oknu

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