Concordance between enzyme activity and genotype of glutathione S-transferase theta (GSTT1).
Blood samples from 140 healthy German volunteers were used to further characterize the genetic polymorphism of the human theta class glutathione S-transferase 1 (GSTT1). For measurements of GSTT1 activity, hemolysates were incubated in vitro with different concentrations of dichloromethane. The resulting enzymatically mediated production of formaldehyde was determined colorimetrically by the Nash reaction. GSTT1 genotyping was performed by polymerase chain reaction (PCR) methods using genomic DNA from total white blood cells. The prevalence of homozygous deletion of the GSTT1 gene was 19.3% (95% confidence limits: 12.2-27.7%). There was a high agreement between genotyping and phenotyping data. The individuals with the null genotype had a rate of formaldehyde production below the limit of quantification. In addition, in the group of GSTT1-positive individuals, we could differentiate highly active people (35.7%) from individuals with an intermediate enzyme activity (45.0%). It can be concluded that the PCR method is suitable to quickly genotype large populations, whereas the phenotyping assay at present offers the advantage of differentiating heterozygously from homozygously active subjects. Our results confirm the ethnic differences in the prevalence of the homozygous deleted genotype which were previously observed and seem to exist even between closely related ethnic groups such as German and Swedish populations.
Bruhn
C
C
Institute of Pharmacy, University Clinic Charite, Humboldt University of Berlin, Germany.
Brockmöller
J
J
Kerb
R
R
Roots
I
I
Borchert
H H
HH
D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male
C413545:glutathione S-transferase T1; D005982:Glutathione Transferase