-Pupose. Systemic Lupus Erythematosus (SLE) is a multifactoral chronic autoimmune disease with unidentified etiology. Imbalance of oxidative status is one possible cause of active disease. Plasma malondialdehyde (MDA) and plasma glutathione (GSH) level have been used as a determinate of oxidative status. Limited data has examined these 2 parameters by severity of SLE. Methods. We determined whether there was an association between plasma MDA and plasma GSH level with the severity of SLE. Forty four SLE patients (2 Men and 42 Women) and twenty healthy volunteers (3 Men, 17 women) participated in this study. SLE participants were classified by the severity of disease (mild, moderate or severe). The plasma MDA and plasma Glutathione levels were measured. The correlation of plasma MDA and plasma GSH levels with the severity of SLE disease were determined. Results. Plasma MDA levels with different severity of SLE (mild, moderate, and severe of SLE patients) were not significantly different from those of the control group (p=1.0).Plasma GSH levels were significantly lower in the moderate and severe SLE groups than the control group (p=0.001). In addition, a significant correlation between plasma GSH and severity of SLE was observed. (Pearson correlation coefficient = -0.428, p <0.001). The relationship could be described by the equation GSH level (μM) = (-7.624) SLEDAI score + 545.90. Conclusion. A significant correlation between plasma GSH and SLE severity exists that may aid evaluation of the disease severity and usefulness of the treatment of SLE.

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BackgroundTamoxifen (TAM) is used in breast cancer treatment, but interindividual variabilities in TAM-metabolizing enzymes exist and have been linked to single nucleotide polymorphisms in the respective encoding genes. The different alleles and genotypes of these genes have been presented for Caucasians and Asians. This study aimed to explore the prevalence of the incomplete functional alleles and genotypes of the CYP2D6 and CYP3A5 genes in Thai breast cancer patients undergoing TAM treatment.Patients and methodsIn total, 134 Thai breast cancer patients were randomly invited to join the Thai Tamoxifen Project. Their blood samples were collected and extracted for individual DNA. The alleles and genotypes were determined by real-time polymerase chain reaction with TaqMan® Drug Metabolism Genotyping Assays.ResultsThe patients were aged from 27.0 years to 82.0 years with a body mass index range from 15.4 to 40.0, with the majority (103/134) in the early stage (stages 0–II) of breast cancer. The median duration of TAM administration was 17.2 months (interquartile range 16.1 months). Most (53%) of the patients were premenopausal with an estrogen receptor (ER) and progesterone receptor (PR) status of ER+/PR+ (71.7%), ER+/PR− (26.9%), ER−/PR+ (0.7%), and ER−/PR− (0.7%). The allele frequencies of CYP2D6*1, CYP2D6*2, CYP2D6*4, CYP2D6*10, CYP3A5*1, and CYP3A5*3 were 72.9%, 3.2%, 1.1%, 22.8%, 37.3%, and 62.7%, respectively, while the genotype frequencies of CYP2D6*1/*1, CYP2D6*1/*2, CYP2D6*2/*2, CYP2D6*4/*4, CYP2D6*1/*10, CYP2D6*2/*10, CYP2D6*4/*10, CYP2D6*10/*10, CYP3A5*1/*1, CYP3A5*1/*3, and CYP3A5*3/*3 were 9.7%, 2.2%, 3.7%, 1.5%, 15.7%, 9.7%, 3.7%, 53.7%, 13.4%, 47.8%, and 38.8%, respectively.ConclusionThe majority (97.8%) of Thai breast cancer patients undergoing TAM treatment carry at least one incomplete functional allele, including 20.9% of the patients who carry only incomplete functional alleles for both the CYP2D6 and CYP3A5 genes. This research indicates the high prevalence of these defective alleles that are involved in TAM-metabolic pathways that might further affect TAM treatment.

We investigated the influence of genetic polymorphisms of CYP2C9 and VKORC1 genotypes on the pharmacokinetics and pharmacodynamics of warfarin and established an equation for predicting the maintenance dose of warfarin in the Thai population using genetic and non-genetic factors. The CYP2C9*2, CYP2C9*3, VKORC1 C1173T and VKORC1 G-1639A genotypes were detected by realtime PCR using fluorogenic hybridization probes. The associations between genetic and demographic factors with respect to warfarin dosage were analyzed. CYP2C9 polymorphisms affect warfarin metabolism as shown by a significant difference in warfarin clearance, whereas VKORC1 genotypes cause a significant difference in warfarin sensitivity index (INR:Cp). The mean weekly warfarin dose was significantly different among different VKORC1 and CYP2C9 genotypes. Patients with the VKORC1 BB haplotype and CYP2C9*1/*1 required about twice the warfarin dose compared to those with the VKORC1 AA haplotype and CYP2C9*1/*1. Using stepwise multiple linear regression, clinical factors (age and weight) and genetic factors (CYP2C9 and VKORC1) could explain about 53.8% of the variance of the warfarin maintenance dose. CYP2C9 and VKORC1 genotypes played an important role in the inter-individual variation in warfarin maintenance dose in a Thai population.

Higher percentages of patients could meet the treatment goal when their plasma oxypurinol concentrations were higher than the proposed therapeutic range for patients with normal renal function.