Opposite Effects of GSTM1 – and GSTT1 – Gene Deletion Variants on Bone Mineral Density

نویسندگان

  • Simona Jurkovic Mlakar
  • Josko Osredkar
  • Janez Prezelj
  • Janja Marc
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Investigation of the Relationship between Genetic Polymorphisms in GSTM1 and GSTT1 Genes and Susceptibility to Lung Functional Abnormalities in Workers Exposed to Air Pollutants at Isfahan Steel Plant

Introduction: Gaseous air pollutants can cause oxidative stress, which can lead to lung damage by inducing inflammation. Polymorphisms in the glutathione S-transferase (GST) gene are involved in the pathogenesis of many diseases, including lung disease. Two glutathione S-transferase Mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) genes belong to this family, in which deletions occur ...

متن کامل

Investigating the rate of glutathione S-transferase T1 and M1 genes deletion in patients with lung cancer

Introduction: Glutathione S-tarnsferases (GST) gene family is one of the enzymes which is responsible for detoxifying mutagens and Carcinogens chemicals. People with null genotype of GSTM1 and GSTT1 genes are at higher risk of developing cancer, especially those who are related to smoking. The goal of this study was investigating the rate of glutathione S-transferase T1 and M1 genes deletion an...

متن کامل

No association between GSTM1 and GSTT1 genetic polymorphisms and susceptibility to opium sap dependence

Glutathione S-transferases (GSTs; EC: 2.5.1.18) are a ubiquitous family of eukaryotic and prokaryotic phase II metabolic isozymes. Genes encoding GSTM1 (OMIM: 138350), and GSTT1 (OMIM: 600436) are members of class mu and theta, respectively. The most common polymorphism in the GSTM1 is a deletion of the whole GSTM1 gene with a lack of enzyme activity. A homozygous deletion in the GSTT1 has also...

متن کامل

Genetic polymorphisms of glutathione-s-transferase M1 and T1 genes with risk of diabetic retinopathy in Iranian population

Objective(s):To the best of our knowledge, this is the first report on the contributions of GST genetic variants to the risk of diabetic retinopathy in an Iranian population. Therefore, the objective of this study was to determine whether sequence variation in glutathione S-transferase gene (GSTM1 and GSTT1) is associated with development of diabetic retinopathy in type 2 diabetes mellitus (T2D...

متن کامل

A cross-sectional study of self-reported chemical-related sensitivity is associated with gene variants of drug-metabolizing enzymes

BACKGROUND N-acetyltransferases (NAT) and glutathione S-transferases (GST) are involved in the metabolism of several ubiquitous chemical substances leading to the activation and detoxification of carcinogenic heterocyclic and aromatic amines. Since polymorphisms within these genes are described to influence the metabolism of ubiquitous chemicals, we conducted the present study to determine if i...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 31  شماره 

صفحات  -

تاریخ انتشار 2011