Opposite Effects ofGSTM1– andGSTT1– Gene Deletion Variants on Bone Mineral Density

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 proposedGSTM1andGSTT1genes as candidates for studying the genetics of osteoporosis.The aim of the present study was to examine possible association ofGSTM1andGSTT1gene 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.GSTM1andGSTT1gene deletion polymorphisms in 712 elderly people were analyzed using the triplex PCR method for the presence ofGSTM1andGSTT1gene 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 ofGSTT1gene deletion polymorphism. ForGSTM1gene deletion polymorphism borderline significant association was found with BMD_ls (p= 0.100). Furthermore, subjects with homozygous deletion ofGSTT1gene showed higher BMD values on all measured skeletal sites and, in contrast, subjects with homozygous deletion ofGSTM1gene showed lower BMD values. Moreover, a gene-gene interaction study showed significant association ofGSTM1-null andGSTT1-null polymorphisms with BMD_ls values (p= 0.044). Carriers with a combination of the presence ofGSTT1gene and the homozygous absence ofGSTM1gene fragment were associated with the lower BMD values at all skeletal sites.The significant association of combination ofGSTT1gene presence and homozygous absence ofGSTM1gene with BMD was demonstrated, suggesting that it could be used, if validated in other studies, as genetic marker for low BMD.