Affiliations: Department of Clinical Biochemistry, Faculty of
Pharmacy, University of Ljubljana, Ljubljana, Slovenia | Department of Endocrinology, Diabetes and Metabolic
Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia | Institute of Clinical Chemistry and Biochemistry,
University Medical Centre Ljubljana, 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: [email protected]
Abstract: Oxidative stress is associated with osteoporosis. The glutathione
S-transferases form the major detoxifying group of enzymes responsible for
eliminating products of oxidative stress. We have therefore proposed
GSTM1 and GSTT1 genes as candidates for studying the genetics of
osteoporosis. The aim of the present study was to examine possible association
of GSTM1 and GSTT1 gene deletion polymorphisms, alone or in
combination, with bone mineral density at femoral neck (BMD_fn), lumbar
spine (BMD_ls) and total hip (BMD_th) in Slovenian elderly women and men. GSTM1 and GSTT1 gene deletion polymorphisms in 712 elderly people
were analyzed using the triplex PCR method for the presence of GSTM1 and
GSTT1 gene segments. BMD_fn, BMD_ls and BMD_th were measured by
the dual-energy X-ray absorptiometry (DEXA) method. Results were analyzed using
univariate statistic model adjusted for sex, body mass index (BMI) and age. Our results showed the significant differences in BMD_th, BMD_ls and
BMD_fn values (p=0.031, 0.017 and 0.023, respectively)
in subgroups of GSTT1 gene deletion polymorphism. For GSTM1 gene
deletion polymorphism borderline significant association was found with
BMD_ls (p=0.100). Furthermore, subjects with homozygous
deletion of GSTT1 gene showed higher BMD values on all measured skeletal
sites and, in contrast, subjects with homozygous deletion of GSTM1 gene
showed lower BMD values. Moreover, a gene-gene interaction study showed
significant association of GSTM1-null and GSTT1-null polymorphisms with
BMD_ls values (p=0.044). Carriers with a combination of
the presence of GSTT1 gene and the homozygous absence of GSTM1 gene
fragment were associated with the lower BMD values at all skeletal sites. The significant association of combination of GSTT1 gene presence and
homozygous absence of GSTM1 gene with BMD was demonstrated, suggesting
that it could be used, if validated in other studies, as genetic marker for low BMD.
Keywords: Osteoporosis, oxidative stress, antioxidant defence system, bone mineral density, triplex method, glutathione s-transferase
