Allele frequencies for glutathione S-transferase and N-acetyltransferase 2 differ in African population groups and may be associated with oesophageal cancer or tuberculosis incidence.
Glutathione S-transferase (GST) and arylamine N-acetyltransferase 2 (NAT2) metabolise many environmental and chemotherapeutic agents, which influence susceptibility to disease. Polymorphisms in these enzymes result in different host phenotypes and contribute to different disease profiles or responses to toxic or chemotherapeutic agents, depending on their frequency in different populations. GST and NAT2 polymorphisms were investigated in different population groups, including African populations, and a range of allelic frequencies have been observed. The GSTM1 null genotype frequency, reported in this paper in two South African ethnic groups, is the lowest reported (0.19-0.21). In contrast, these same groups have a high GSTT1 null frequency (0.41-0.54), which is considerably higher than in African-Americans, or other Africans. The GSTT1 null frequency is comparable to the Chinese, a population with a very high oesophageal cancer incidence, similar to that in the African group. The frequency of the GSTPi Val105 variant in the South African Xhosas was also high (0.53), differing significantly from the low frequency in other Africans. These variants could therefore be associated with high cancer susceptibility. In addition, the high proportion of NAT2 "fast" alleles may partially explain the high tuberculosis prevalence in South Africans, due to reduced isoniazid efficacy in the presence of rapid acetylation.
Department of Medical Biochemistry, MRC Centre for Molecular & Cellular Biology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Craig H
CH
Adams
Cedric J
CJ
Werely
Thomas C
TC
Victor
Eileen G
EG
Hoal
Gawie
G
Rossouw
Paul D
PD
van Helden
D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D015331:Cohort Studies; D017931:DNA Primers / Q000737:chemistry; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007527:Isoenzymes / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D014376:Tuberculosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D001741:Black or African American
D001191:Arylamine N-Acetyltransferase; D017931:DNA Primers; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human