Genetic polymorphism of cytochrome P450 1A1 (Cyp1A1) and glutathione transferases (M1, T1 and P1) among Africans.
The co-ordinate expression and regulation of the drug metabolising enzymes, cytochrome P4501A1 (CYPlAl) and glutathione transferases (GSTM1, GSTT1 and GSTP1), and their metabolic balance in the cells of target organs may determine whether exposure to carcinogens results in cancer. Besides showing variability in activity due to induction and inhibition, these enzymes also exhibit genetic polymorphism that alter enzyme levels and activity. We determined frequencies of common allelic variants of CYP1A1 and glutathione (M1, T1 and P1) among Tanzanians, South African Venda and Zimbabweans using PCR/restriction fragment length polymorphism techniques. The CYP1A1 Val462 mutant variant was found at a frequency of 1.3% among 114 subjects. The GSTM1*0 genotype was found at a frequency of 29% and 33% among Tanzanian psychiatric patients and healthy volunteers, respectively. Similarly, the GSTT1*0 polymorphism was present with a frequency of 25% in both the psychiatric patients and healthy controls. The frequency of GSTP1 Val105 variant was 16%, 12% and 21% among Tanzanians, South African Venda and Zimbabweans, respectively. We conclude here that CYP1A1 Val462 polymorphism is very rare among Africans. This is the first report of the GSTP1 Val105 variant frequency in African populations. We show here that there are no differences in frequencies of the variant alleles for CYP1A1, GSTM1, GSTT1 and GSTP1 in the three African populations.
Dandara
Collet
C
Department of Biochemistry, University of Zimbabwe, Harare. collet@xenobiot.icon.co.zw
Sayi
Jane
J
Masimirembwa
Collen M
CM
Magimba
Ayoub
A
Kaaya
Sylvia
S
De Sommers
Kierk
K
Snyman
Jacques René
JR
Hasler
Julia A
JA
D000349:Africa; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000097:blood / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000097:blood / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000235:genetics; D001523:Mental Disorders / Q000097:blood / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
D004273:DNA, Neoplasm; D007527:Isoenzymes; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase