Testing GSTP1 genotypes and haplotypes interactions in Slovenian post-/pre-menopausal women: Novel involvement of glutathione S-transferases in bone remodeling process
Jurković Mlakar, Simona (Author), Preželj, Janez (Author), Marc, Janja (Author)

URLURL - Presentation file, Visit http://www.sciencedirect.com/science/article/pii/S0378512211004087# This link opens in a new window

Objectives Osteoporosis (OP) is an age-related disease associated with increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense system, such as low activity of glutathione S-transferase (GST) family. The enzyme activity of the member of GSTs, GSTP1, depends on gene polymorphisms such as: Ala114Val and Ile105Val. The aim of this study was to evaluate the association between genetic polymorphisms of the GSTP1 gene and BMD variation and biochemical bone remodeling markers in 523 Slovenian pre- and post-menopausal women. Study design Observational pilot study in a representative cohort of Slovenian patients with adjustment for potential confounders (age, height, weight, years since menopause, smoking status and glucocorticoid use) using univariate one-way and two-way analyses. Main outcome measures Ala114Val and Ile105Val polymorphisms genotypes of GSTP1 gene, bone mineral density (BMD) values of total hip (_th), femoral neck(_fn) and lumbar spine (_ls), plasma osteocalcin (OC), serum bone alkaline phosphatase (BALP), free soluble RANKL and serum osteoprotegerin (sOPG) concentrations were determined. Results Our results show that the Ala114Val heterozygotes are (borderline) significantly associated with higher concentrations of pOC (p=0.052) and decreased BMD_fn values (p=0.053) and the same trend is shown for BMD_th and BMD_ls values in osteopenic postmenopausal women. Furthermore, significantly higher concentrations of pOC were determinedamong Val allele carriers of Ile105Val gene polymorphism (p=0.037) and in carriers with the absent 114Ala-105Ile haplotype combination, again in osteopenic post-menopausal women. In addition, in pre-menopausal women the significant associations between sOPG and Ala114Val genotypes subgroups and between sBALP and Ile105Val genotypes subgroups, alone or in combination with Ala114Val, were determined (0.032, 0.026 and 0.008, respectively). Conclusions Since significant associations existed in Ala114Val genotype and 114Ala-105Ile haplotype subgroups, these variations can be useful for determining low BMD and high pOC risk in postmenopausal women.

Keywords:GSTP1 genotip, osteoporoza, Ala114Va, kostna mineralna gostota
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Number of pages:str. 180-187
Numbering:Vol. 71, no. 2
ISSN on article:0378-5122
DOI:10.1016/j.maturitas.2011.11.023 Link is opened in a new window
COBISS.SI-ID:3185521 Link is opened in a new window
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Shortened title:Maturitas
COBISS.SI-ID:25916160 This link opens in a new window

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