Glutathione-S-transferase polymorphism, metallothionein expression, and mercury levels among students in Austria.

BACKGROUND: Detoxification is an essential process in all living organisms. Humans accumulate heavy metals primarily as a result of lifestyle and environmental contamination. However, not all humans experience the estimated individual exposure. This suggests the presence of genetic regulatory mechanisms. OBJECTIVE: In order to identify genetic factors underlying the inter-individual variance in detoxification capacity for the heavy metal mercury, 192 students were investigated. We focused on the relationship between polymorphisms in glutathione-S-transferase (GST) genes and mercury concentrations in blood, urine, and hair. The correlation between blood mercury levels, GSTT1 and GSTM1 polymorphism, and gene expression of certain metallothionein subgroups (MT1, MT3) was evaluated in a further group of students (N=30). METHODS: Mercury levels in acid digested samples were measured by cold vapor AAS. Genotyping of the GSTT1 and GSTM1-gene deletion polymorphism was performed by means of PCR. Gene expression of several MT genes was analyzed in lymphocytes from fresh peripheral blood by semiquantitative RT-PCR. RESULTS: The following was noted: a) hair mercury concentrations are significantly increased in persons with the double deleted genotype (GSTT1-/- and GSTM1-/-) as compared to persons with the intact genotype, and b) MT1X expression is higher in persons with the intact genotype (GSTT1+/+ and GSTM1+/+). CONCLUSIONS: We conclude that the epistatic effect of the GSTT1 and the GSTM1 deletion polymorphism is a risk factor for increased susceptibility to mercury exposure. The relationship between MT gene expression and GST gene polymorphisms needs further investigation. If MT expression depends on GST polymorphisms it would have important implications on the overall metal detoxification capability of the human organism.

Transcriptional profiles from patients with dystrophinopathies and limb girdle muscular dystrophies as determined by qRT-PCR.

Mutations in genes coding for the dystrophin-glycoprotein complex (DGC) cause inherited muscular dystrophies (MD), including Morbus Duchenne (DMD) and M. Becker (BMB) as well as limb-girdle muscular dystrophies (LGMD). New insights into the pathophysiology of the dystrophic muscle, the identification of compensatory mechanisms and additional proteins interacting with dystrophin are essential for developing new treatments. In order to define molecular mechanisms induced by lack of dystrophin and the subsequent counter-regulatory transcriptional response of degenerating muscle fibres, we have investigated the mRNA expression of 19 functionally linked genes in biopsies of patients with MD by means of real time qRT-PCR. Our results define a uniform transcriptional profile of the dystrophic muscle characterized by degeneration and regeneration. Several genes encoding structural proteins appear remarkably highly expressed.