Genetic background of lead and mercury metabolism in a group of medical students in Austria.
BACKGROUND
Information on the impact of genetic predisposition on metal toxicokinetics in the human body is limited. There is increasing evidence that certain genetic polymorphisms modify lead and mercury toxicokinetics. This called for analysis of further candidate genes.


OBJECTIVE
Medical students (N=324) were examined in order to detect potential associations between lead exposure and polymorphisms in HFE, VDR, ALAD, and MT genes, as well as between mercury exposure and GSTT1, GSTM1, GSTA1, GSTP1, GCLC, and MT polymorphisms.


METHODS
The levels of lead and mercury exposure of students were determined by blood, urine, and hair analyses (ICP-MS, CV-AAS). Genotyping of common polymorphisms was examined by MALDI-TOF MS and the TaqMan methodology. Associations between lead and mercury exposures and genetic background were examined by bivariate analysis, and by categorical regression analysis (CATREG) controlled by metal- and matrix-specific variables.


RESULTS
Lead and mercury levels in urine, blood, and hair indicated low exposures. VDR polymorphism and joint presence of VDR/ALAD polymorphisms were significantly and independently associated with urine lead concentrations (CATREG P<0.05). Polymorphisms in GSTP1-114 and MT4 genes as well as dual gene combinations including GSTP1, GCLC, GSTT1, and GSTM1 polymorphisms were independent variables related to mercury body burdens (CATREG P<0.05). GSTP1-114/GSTT1 and GSTP1-105/GCLC combinations showed synergistic effects on hair mercury levels compared to single-gene variants.


CONCLUSIONS
We found evidence that certain genetic backgrounds were associated with lead and mercury metabolism, suggesting gene-environment and gene-gene-environment interactions. The modes of interaction remain to be evaluated.
Gundacker
Claudia
C
Medical University of Vienna, Center for Public Health, Lab Ecotoxicology, Waehringer Strasse 10, A-1090 Vienna, Austria. claudia.gundacker@meduniwien.ac.at
Wittmann
Karl J
KJ
Kukuckova
Martina
M
Komarnicki
Günter
G
Hikkel
Imrich
I
Gencik
Martin
M
D000328:Adult; D001317:Austria; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D005787:Gene Frequency; D006197:Hair / Q000737:chemistry; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008628:Mercury / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011110:Polymorphism, Genetic; D013337:Students, Medical; D055815:Young Adult
D004785:Environmental Pollutants; D007854:Lead; D004247:DNA; D008628:Mercury