and seven sequence changes in the promoter region. No relationship between
any of the identified SNPs was observed in the liver bank with either GSTA1
function or expression. In 48 Caucasian human liver samples, this variant was
present in 47.9% of the samples. Matsuno et al. genotyped 147 healthy
Japanese subjects and found 70.7% were^ A/^ A; 26.5%^ A/^ B, and 2.7%^ B/^ B
(allele frequency 0.16) (Table 3.11) (Matsuno et al., 2004).
3.3.7 GST Mu Class
3.3.7.1 Overview The GSTM1 through GSTM5 gene locus is on chromo-
some 1p spanning 100 kB. Deletion of the GSTM1 gene (null phenotype) is
relatively common (70% allele frequency in Caucasians and Asians, 50% in
Africans). Given the protective role of GST against environmentally
bioactivated carcinogens, many genetic polymorphism studies have been
done with regard to cancer incidence. Polymorphisms in other GSTM enzymes
have also been identified, especially with GSTM3. One mutation of GSTM3 is
an insertion of three base pair sequence that generates a transcription factor
binding site for ying yang 1 (GSTM3 AA). It is believed that the presence of the
YY1 transcription factor acts as an inducer. GSTM3 is expressed in higher
amounts in lung than GSTM1. It is also expressed in significant amounts in
astrocytes in the blood-brain barrier and in brain tissue.
TABLE 3.10 Distribution of the C–69T hGSTA1 genotypes in control populations.
Population N A/A A/B B/B
African-American 70 0.61 0.26 0.13
African-American women 52 0.63 0.26 0.12
Caucasian 278 0.38 0.48 0.14
Caucasian men 162 0.35 0.52 0.13
Caucasian women 116 0.41 0.44 0.16
Hispanic women 53 0.36 0.51 0.13
TABLE 3.11 Frequency distributions of GST1A1 and GSTT1 genotypes 147
Japanese subjects.
GSTA1 GSTT1(^) A/ (^) A (^) A/ (^) B (^) B/ (^) B (^) A/ (^) A (^) A/ (^0) A/ (^0)
N 104 39 4 9 67 71
Observed
frequency (%)
70.7 26.5 2.7 6.1 45.6 48.3
95% CI 62.9–77.5 20.1–34.2 1.1–6.8 3.3–11.2 37.7–53.6 40.4–56.3
Expected
frequency (%)
71.2 26.3 2.4 8.4 41.1 50.6
(Adapted from Coles et al., 2001).
GLUTATHIONE-S-TRANSFERASES 77