Background: The glutathione S-transferase (GST) superfamily comprises multiple isozymes with compelling evidence of functional polymorphisms in various ethnic groups. All these mutations, in particular those in class A, k and u GST, are likely to contribute to interindividual differences in responses to xenobiotics including response to chemotherapy and associated with altered disease. The frequency of common GST mutations in Uygur Chinese is unknown. We investigated the common mutations of GSTM1, GSTT1, and GSTP1 in Uygur (N =154) Chinese and compare with Han Chinese (N =196). Method: GSTM1 and GSTT1 polymorphisms were analyzed by multiplexed PCR, and GSTP1 polymorphism was detected by PCR-based restriction fragment length polymorphism (RFLP) analysis. Results: GSTM1 null genotype was found in 53.2% Uygur Chinese, which was close to that in Han Chinese (56.1%) ( P=0.592). A significantly lower frequency ( P <0.05) of GSTT1 null genotype in Uygur Chinese (26.6%) was observed compared with Han Chinese (50.0%). Uygur Chinese exhibited a GSTP1 genotype distribution of 51.3% I/I, 40.2% I/V and 8.4% V/V, which was different from that in Han Chinese (60.7% I/I, 35.2% I/V and 4.1% V/V). Conclusions: There is marked ethnic difference in the frequency of common GSTT1 and GSTP1 mutation, but not GSTM1 mutation, between Uygur and Han Chinese. D 2005 Elsevier B.V. All rights reserved.

In vitro and in vivo studies have indicated that the induction or inhibition of cytochrome P450 (CYP) is one of the major mechanisms for some clinically important pharmacokinetic herb-drug interactions. An attempt was made to simulate the effects of herbal preparation with single or multiple CYP-inhibiting constituents on the area of the plasma concentration-time curve (AUC) of coadministered drug that was either a low clearance drug by intravenous (i.v.) injection or a high clearance drug by oral route. Our simulation studies indicated that the expected increase (Rc) in the AUC of the coadministered drug by inhibiting herbal constituent(s) was dependent on the route of administration. For low clearance drug by i.v. injection, Rc was generally determined by inhibition constant (Ki), unbound inhibitor concentration ([I]), hepatic fraction (fh), number of inhibitory herbal constituents (n) and metabolic pathway fraction in hepatic metabolism (fm), while Rc for a high clearance drug by oral route, Rc was determined by Ki, [I], n and fm. By varying these parameters, Rc changed accordingly. It appeared likely to predict a herb-drug metabolic interaction, if the inhibiting herbal constituents could be quantitatively determined. However, many herb- and drug-related factors may cause difficulties with the prediction, and thus in vivo animal and human studies are always necessary. Copyright

Objective. This study was conducted to investigate the thiopurine S-methyltransferase (TPMT) activity distribution and gene mutations in Kazaks, and compared the results with those of other ethnic groups. Methods. Erythrocyte TPMT activity was measured in Kazaks (n=327) via a validated highperformance liquid chromatography assay. Polymerase chain reaction-based methods were used to analyze three commonly reporter-inactivating mutations: G238C, G460A, and A719G. Results. Unimodal distribution of TPMT activity was found in Kazaks. Six TPMT*3C heterozygotes and two TPMT*3A heterozygotes were found in 327 Kazaks, with allele frequencies of 0.9 and 0.3%, respectively. The subjects with TPMT*3A and TPMT*3C heterogygotes had substantial TPMT activity over the range of 6.40Y11.75 U/ml RBC. Conclusion. Unlike in most Caucasians, TPMT*3C is a common mutant allele in Kazaks, whereas TPMT*3A is a rare mutant allele. Further studies are needed to explore the clinical impact of these TPMT mutants to thiopurine therapy in Kazak patients.