Affiliations: University Medical Centre Ljubljana, Institute of
Clinical Chemistry and Biochemistry, Ljubljana, Slovenia | University Medical Centre Ljubljana, Department of
Endocrinology, Diabetes and Metabolic Diseases, Ljubljana, Slovenia | University of Ljubljana, Faculty of Pharmacy,
Department of Clinical Biochemistry, Ljubljana, Slovenia
Note: [] Corresponding author: Prof. Dr. Janja Marc, MPharm, Department
of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana,
Askerceva cesta 7, SI-1000 Ljubljana, Slovenia. Tel.: +386 1 4769 600; Fax:
+386 1 4258 031; E-mail: janja.marc@ffa.uni-lj.si
Abstract: Recently, oxidative stress has been suggested as participating in
the development of osteoporosis. Glutathione peroxidase 1 (GPX1) is one of
antioxidant enzymes responsible for the defence of cells against oxidative
damage and thus for protection against age related diseases such as
osteoporosis. The aim of present study was to associate genetic variances of GPX1
enzyme with bone mineral density (BMD) and biochemical bone turnover markers
and to show the influence of antioxidative defence system in genetics of
osteoporosis. We evaluated 682 Slovenian subjects: 571 elderly women and 111
elderly men. All subjects were genotyped for the presence of GPX1 gene
polymorphisms Pro198Leu and polyAla region. BMD and biochemical markers were
also measured. General linear model analysis, adjusted to height, and (one-way)
analysis of variance were used to assess differences between the genotype.and
haplotype subgroups, respectively. The significant or borderline significant associations were found
between the polyAla or the Pro198Leu polymorphisms and total hip BMD (0.018;
0.023, respectively), femoral neck BMD (0.117; 0.026, respectively) and lumbar
spine BMD (0.032; 0.086, respectively), and with biochemical bone turnover
markers such as plasma osteocalcin (0.027; 0.025, respectively) and serum
C-terminal telopeptide of type I collagen concentrations (0.114; 0.012,
respectively) in whole group. Haplotype analysis revealed that the 6-T
haplotype is associated significantly with low BMD values (p< 0.025) at all
measured locations of the skeleton, and with high plasma osteocalcin
concentrations (p=0.008). This study shows for the first time that the polymorphisms polyAla
and Pro198Leu of the GPX1 gene, individually and in combination, are associated
with BMD and therefore may be useful as genetic markers for bone disease.
Moreover, it implies the important contribution of the oxidative stress to
pathogenesis of osteoporosis.
Keywords: Osteoporosis, oxidative stress, glutathione peroxidase 1, bone mineral density, osteocalcin
