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.
Gundacker
Claudia
C
Medical University of Vienna, Center for Public Health, Dept. of Ecotoxicology, Waehringer Strasse 10, A-1090 Vienna, Austria. claudia.gundacker@meduniwien.ac.at
Komarnicki
Günter
G
Jagiello
Peter
P
Gencikova
Alexandra
A
Dahmen
Norbert
N
Wittmann
Karl J
KJ
Gencik
Martin
M
D000818:Animals; D001317:Austria; D003430:Cross-Sectional Studies; D004843:Epistasis, Genetic; D005247:Feeding Behavior; D005260:Female; D005399:Fishes; D020387:Food Chain; D005506:Food Contamination; D017353:Gene Deletion; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics*; D006197:Hair / Q000737:chemistry; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008628:Mercury / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008668:Metallothionein / Q000235:genetics*; D011110:Polymorphism, Genetic
D005982:Glutathione Transferase; D008628:Mercury; D008668:Metallothionein; C413545:glutathione S-transferase T1