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

Zhong, Shi-long, Zhou, Shu-Feng, Chen, Xiao, Chan, Sui Yung, Chan, Eli, Ng, Ka-Yun, Duan, Wei and Huang, Min 2006, Relationship between genotype and enzyme activity of glutathione S-transferases M1 and P1 in Chinese, European journal of pharmaceutical sciences, vol. 28, no. 1-2, pp. 77-85.

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Title Relationship between genotype and enzyme activity of glutathione S-transferases M1 and P1 in Chinese
Author(s) Zhong, Shi-long
Zhou, Shu-Feng
Chen, Xiao
Chan, Sui Yung
Chan, Eli
Ng, Ka-Yun
Duan, Wei
Huang, Min
Journal name European journal of pharmaceutical sciences
Volume number 28
Issue number 1-2
Start page 77
End page 85
Publisher Elsevier B.V.
Place of publication Amsterdam, The Nertherlands
Publication date 2006-05
ISSN 0928-0987
Keyword(s) glutathione S-transferase M1 and P1
polymorphism
erythrocyte
Chinese
Summary Glutathione S-transferases (GSTs) are the major detoxifying Phase II enzyme for eliminating electrophilic compounds. Mutations in GSTM1, GSTP1 and GSTT1 in Caucasian and GSTA1 in Chinese have been found to reduce enzyme activity. However, data on the impact of common genetic polymorphisms of GSTM1 and GSTP1 on enzyme activity in Chinese is lacking. This study aimed to investigate the effect of common GSTP1 and GSTM1 polymorphisms on erythrocyte GST activity in healthy Chinese (n = 196). GSTM1 null mutation (GSTM1*0) was analyzed by a PCR-Multiplex procedure, whereas GSTP1 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 GSTM1 null genotype was 54.3% and the frequency of GSTP1-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 GSTP1*-Ile/Val genotype group (3.53 ± 0.63 U/g Hb) was significantly lower than that for subjects with GSTP1-Ile/Ile genotype (4.25 ± 1.07 U/g Hb, P = 0.004), while subjects with the GSTP1-Val/Val genotype had the lowest enzyme activity (2.44 ± 0.67 U/g Hb). In addition, the GST activity in carriers of GSTM1*0/GSTP1-Ile/Ile was significantly higher than that of subjects inherited GSTM1*0/GSTP1-Ile/Val or GSTM1*0/GSTP1-Val/Val. However, there is no association between GSTM1 null mutation and reduced enzyme activity. GSTP1 codon 105 mutation led to reduced erythrocyte GST activity in Chinese. A combined GSTP1 and GSTM1 null mutations also resulted in significantly reduced GST activity. Further studies are needed to explore the clinical implications of GSTM1 and GSTP1 polymorphisms.
Language eng
Field of Research 111502 Clinical Pharmacology and Therapeutics
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006 Elsevier B.V.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30009281

Document type: Journal Article
Collection: School of Medicine
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