Phenotyping of the glutathione S-transferase M1 polymorphism in Zimbabweans and the effects of chloroquine on blood glutathione S-transferases M1 and A.
The frequency of the null allele phenotype of glutathione S-transferase (GST) M1 was investigated in 114 Zimbabweans and results for a subset of 63 subjects were compared with genotyping by PCR. In addition, the effect of the antimalarial chloroquine on blood levels of GSTM1 and GSTA in 19 subjects was studied. Quantification of GSTs was by enzyme linked immunosorbent assays (ELISA). Thirty percent of the subjects were of the GSTM1 null phenotype. Comparison of results of phenotyping by ELISA and genotyping by PCR showed that 16% of samples were in discordance; unknown mutations in the GSTM1 gene in the Zimbabwean population may explain this observation. Chloroquine decreased levels of blood GSTM1 and GSTA by 50% or more. In populations treated with chloroquine, these decreases in GST activities might lead to compromised ability to detoxify xenobiotics, could confound GSTM1 phenotyping and might invalidate use of GSTA as an indicator of liver damage.
Mukanganyama
S
S
Department of Biochemistry, University of Zimbabwe, Harare, Zimbabwe.
Masimirembwa
C M
CM
Naik
Y S
YS
Hasler
J A
JA
D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005982:Glutathione Transferase / Q000097:blood* / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000097:blood* / Q000187:drug effects* / Q000235:genetics; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic
D000962:Antimalarials; D007527:Isoenzymes; D002738:Chloroquine; D005982:Glutathione Transferase