Relationship between genotype and enzyme activity of glutathione S-transferases M1 and P1 in Chinese

Glutathione <i>S</i>-transferases (GSTs) are the major detoxifying Phase II enzyme for eliminating electrophilic compounds. Mutations in <i>GSTM1</i>, <i>GSTP1</i> and <i>GSTT1</i> in Caucasian and <i>GSTA1</i> in Chinese have been found to reduce enzyme activity. However, data on the impact of common genetic polymorphisms of <i>GSTM1</i> and <i>GSTP1</i> on enzyme activity in Chinese is lacking. This study aimed to investigate the effect of common <i>GSTP1</i> and <i>GSTM1</i> polymorphisms on erythrocyte GST activity in healthy Chinese (<i>n</i> = 196). <i>GSTM1 </i>null mutation (<i>GSTM1</i>*0) was analyzed by a PCR-Multiplex procedure, whereas<i> GSTP1</i> 313A → G polymorphism (resulting in Ile105Val at codon 105) was analyzed by PCR-restriction fragment length polymorphism (RFLP) analysis. Erythrocyte GST activity was measured using 1-chloro-2,4-dinitro-bezene (CDNB) as the model substrate. The frequency of <i>GSTM1</i> null genotype was 54.3% and the frequency of <i>GSTP1</i>-Ile/Ile, -Ile/Val, and -Val/Val genotype was 60.7%, 35.2% and 4.1%, respectively, with a frequency of 21.7% for the 105 valine allele. Age, gender and smoking did not significantly affect the erythrocyte GST activities. The mean erythrocyte GST enzyme activity for <i>GSTP1</i>*-Ile/Val genotype group (3.53 ± 0.63 U/g Hb) was significantly lower than that for subjects with <i>GSTP1</i>-Ile/Ile genotype (4.25 ± 1.07 U/g Hb, P = 0.004), while subjects with the <i>GSTP1</i>-Val/Val genotype had the lowest enzyme activity (2.44 ± 0.67 U/g Hb). In addition, the GST activity in carriers of <i>GSTM1</i>*0/<i>GSTP1</i>-Ile/Ile was significantly higher than that of subjects inherited <i>GSTM1</i>*0/<i>GSTP1</i>-Ile/Val or <i>GSTM1</i>*0/<i>GSTP1</i>-Val/Val. However, there is no association between <i>GSTM1</i> null mutation and reduced enzyme activity. <i>GSTP1</i> codon 105 mutation led to reduced erythrocyte GST activity in Chinese. A combined <i>GSTP1</i> and <i>GSTM1</i> null mutations also resulted in significantly reduced GST activity. Further studies are needed to explore the clinical implications of <i>GSTM1 </i>and <i>GSTP1</i> polymorphisms.<br />