Dandara Collet, Sayi Jane, Masimirembwa Collen M, Magimba Ayoub, Kaaya Sylvia, De Sommers Kierk, Snyman Jacques René, Hasler Julia A
Department of Biochemistry, University of Zimbabwe, Harare.
Clin Chem Lab Med. 2002 Sep;40(9):952-7. doi: 10.1515/CCLM.2002.167.
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 GSTM10 genotype was found at a frequency of 29% and 33% among Tanzanian psychiatric patients and healthy volunteers, respectively. Similarly, the GSTT10 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.
药物代谢酶细胞色素P4501A1（CYPlAl）和谷胱甘肽转移酶（GSTM1、GSTT1和GSTP1）的协同表达与调控及其在靶器官细胞中的代谢平衡，可能决定接触致癌物是否会导致癌症。除了因诱导和抑制而表现出活性变异性外，这些酶还表现出改变酶水平和活性的基因多态性。我们使用聚合酶链反应/限制性片段长度多态性技术，测定了坦桑尼亚人、南非文达人和津巴布韦人中CYP1A1和谷胱甘肽（M1、T1和P1）常见等位基因变体的频率。在114名受试者中，发现CYP1A1 Val462突变变体的频率为1.3%。在坦桑尼亚精神病患者和健康志愿者中，GSTM10基因型的频率分别为29%和33%。同样，GSTT10多态性在精神病患者和健康对照中的频率均为25%。GSTP1 Val105变体的频率在坦桑尼亚人、南非文达人及津巴布韦人中分别为16%、12%和21%。我们在此得出结论，CYP1A1 Val462多态性在非洲人中非常罕见。这是关于非洲人群中GSTP1 Val105变体频率的首次报道。我们在此表明，这三个非洲人群中CYP1A1、GSTM1、GSTT1和GSTP1变体等位基因的频率没有差异。
