| 2018 | Effects of ABCB1 rs1045642 polymorphisms on the efficacy and safety of amlodipine therapy in Caucasian patients with stage I-II hypertension. | Pharmgenomics Pers Med | The aim of this study was to determine the impact of (MDR1) polymorphisms on the efficacy and safety of amlodipine in Caucasian patients.The 12-week study included 100 patients. Patients with the newly diagnosed stage I-II hypertension (HT) were recruited to complete genotyping of the single-nucleotide polymorphism (SNP). The study design did not include a control group. Before treatment, all patients either did not undergo antihypertensive treatment at all or did not receive regular antihypertensive therapy. The initial dose was 5 mg/day. Four office blood pressure measurements, two 24-hour noninvasive ambulatory blood pressure measurements, and questionnaires of Tsvetov were used to evaluate the efficacy and safety of amlodipine.The highest antihypertensive effect in combination with the lowest incidence of adverse reactions was observed in the TT group, while patients with the CC genotype showed a low antihypertensive effect and the highest incidence of adverse effects. Patients with the CC genotype presented with adverse effects predominantly in the form of edema. A total of 33 patients reached the target blood pressure (SBP <140 mmHg; DBP <90 mmHg): two patients with the CC genotype (12%); 18 patients with the CT genotype (34%); and 13 patients with the TT genotype (43%). The intergroup differences were: CC vs CT, =0.02; CC vs TT, =0.02; and CT vs TT, =0.05. The results of this study indicate the potential of pharmacogenetic testing for SNP when prescribing amlodipine for the first time in Caucasian patients with stage I-II arterial HT. |
| 2018 | Effect of CYP3 A4, CYP3 A5 and ABCB1 gene polymorphisms on the clinical efficacy of tacrolimus in the treatment of nephrotic syndrome. | BMC Pharmacol Toxicol | The efficacy of tacrolimus (TAC) is variable in the treatment of nephrotic syndrome (NS), which might be related to genetic variation among patients. Therefore, we aim to investigate the effects of CYP3 A4, CYP3 A5 and ABCB1 gene polymorphisms on the clinical efficacy of TAC in the treatment of NS patients. Methods 100 NS patients were treated with TAC and prednisone and followed up for 3 months. Genotype differences (CYP3 A4*1G, CYP3 A5*3, ABCB1 1236C > T and ABCB1 2677G > T/A) were detected by Sanger sequencing. The clinical efficacy was evaluated by the 24 h urinary protein quantitation, albumin, renal function and the degree of edema. Multivariable logistic regression was used to analyze the effect of gene polymorphisms on the clinical efficacy of TAC.There were 35 patients (35%) with complete remission, 43 patients (43%) with partial remission, 22 patients (22%) without remission, and no patients with recurrence. For CYP3A4, there were 56, 42, and 2 patients with *1/*1, *1/*1G and *1G/*1G genotype, respectively. For CYP3A5, there were 8, 36 and 56 cases with*1/*1, *1/*3 and *3/*3 genotype, respectively. For ABCB1 C1236T, there were 10, 44, and 46 cases with 1236CC, 1236CT and 1236TT genotype, respectively. For ABCB1 G2677 T/A, there were 13, 57, and 30 patients with 2677GG genotype, 2677GT/GA genotype and 2677TT/AA/TA genotype, respectively. The mutant allele frequencies of CYP3A4*1G, CYP3A5*3, ABCB1 C1236T and ABCB1 G2677 T/A were 23%, 74%, 68% and 58.5%, respectively. Results reveal that the gene polymorphisms of CYP3A4 and CYP3A5 and CCB do not affect the clinical efficacy of TAC. For ABCB1 C1236T,TT genotype can increase the effectiveness 12.085 times compared with CC and CT genotype (P = 0.018, OR = 12.085, 95%CI 1.535-95.148). For ABCB1 G2677 T/A, the clinical efficacy of patients with mutant genotype is 8.683 times than that of wild-type and heterozygous patients (P = 0.042, OR = 8.683, 95%CI 1.080-69.819). Overweight patients can improve the clinical efficacy by 15.838 times (P = 0.020, OR = 15.838, 95%CI1.550-161.788).ABCB1 C1236T, ABCB1 G2677 T/A genotype and BMI are probably the factors influencing the clinical efficacy of TAC in treating patients with NS. |
| 2017 | Genetic Polymorphisms Contribute to the Individual Variations of Imatinib Mesylate Plasma Levels and Adverse Reactions in Chinese GIST Patients. | Int J Mol Sci | Imatinib mesylate (IM) has dramatically improved the outcomes of gastrointestinal stromal tumor (GIST) patients. However, the clinical responses of IM may considerably vary among single individuals. This study aimed to investigate the influences of genetic polymorphisms of drug-metabolizing enzyme (CYP3A4), transporters (ABCB1, ABCG2), and nuclear receptor (Pregnane X Receptor (PXR, encoded by )) on IM plasma levels and related adverse reactions in Chinese GIST patients. A total of 68 Chinese GIST patients who have received IM 300-600 mg/day were genotyped for six single nucleotide polymorphisms (SNPs) , and the steady-state IM trough plasma concentrations were measured by a validated HPLC method. There were statistically significant variances in the steady-state IM trough plasma concentrations (from 272.22 to 4365.96 ng/mL). Subjects of in , allele carriers in and in had significantly higher steady-state IM dose-adjusted trough plasma concentrations. Subjects of in had significantly higher incidence rate of edema. The genetic polymorphisms of , , were significantly associated with IM plasma levels, and the genetic variations of were significantly associated with the incidence rate of edema in Chinese GIST patients. The current results may serve as valuable fundamental knowledge for IM therapy in Chinese GIST patients. |
| 2017 | Association of the hOCT1/ABCB1 genotype with efficacy and tolerability of imatinib in patients affected by chronic myeloid leukemia. | Cancer Chemother Pharmacol | The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia.Through a procedure based on a sequence of classical statistics methods, we investigated the possible relationships between treatment efficacy/tolerability and combinations of time-independent variables as gender and genetic covariates in the form of single nucleotide polymorphisms (SNPs) or combinations thereof. Moreover, since the drug tolerability has a strong incidence on the discontinuation of the therapy, we investigated whether the time of manifestation of the most frequent toxic effects can be related to time-independent patients' characteristics or not.We found that a combination of two polymorphisms, namely hOCT1 c.480C>G (rs683369) and ABCB1 c.3435C>T (rs1045642), seems to play the role of predictor for imatinib in both efficacy and toxicity. Furthermore, the time of manifestation of edema toxicity is found to be associated to a combination of gender and ABCB1 c.3435C>T, whereas the time of manifestation of cramp toxicity appears related to gender.The novelty of this study is dual: the achievement of results that potentially have a significant clinical interest and the demonstration that the adoption of composed covariates may represent a unique tool to study different aspects of the treatment with imatinib. |
| 2014 | Basal and benzo[a]pyrene-induced expression profile of phase I and II enzymes and ABC transporter mRNA in the early life stage of Chinese rare minnows (Gobiocypris rarus). | Ecotoxicol Environ Saf | ATP-binding cassette (ABC) transporters together with phase I and II detoxification enzymes have been considered as included in a cellular detoxification system. Previous studies have highlighted the involvement of aryl hydrocarbon receptor (AHR) and Cyp1a in PAH-induced embryo toxicity. However, the response of other xenobiotic enzymes/transporters in PAH-mediated embryo toxicity is not fully characterized. In the present study, rare minnow embryos were exposed to 10 and 100µg/L BaP within 4h post-fertilization (hpf) up to 168 hpf. RNA was extracted at 24, 48, 96, and 168 hpf. The basal and BaP-induced expression of phase I enzyme genes (cyp1a, 1b1, and 1c1), phase II enzyme gene (gstm and ugt1a), and ABC transporter genes (abcb1, abcc1, abcc2, and abcg2) mRNA was determined using real-time PCR. Severe developmental defects (e.g., spinal deformities, pericardial and yolk-sac edema) were observed in the BaP treated groups. The basal expression showed that gstm was most strongly expressed, followed by abcb1, ugt1a, and abcc2, whereas cyp1a, 1b1, 1c1, and abcg2 showed weak expression. BaP significantly induced the mRNA expression of three CYP1s (cyp1a, 1b1, and 1c1) (p<0.05) and the ABC transporters (abcc1, abcc2, and abcg2) in a dose-dependent manner. However, the mRNA expression of Phase II enzymes (gstm, ugt1a) for the BaP treatments showed no significant difference with that of the controls. Furthermore, distinct induced patterns of these genes were observed during different exposure periods. Simultaneous up-regulation of the cyp and ABC transporter gene transcripts suggests that a possible involvement and cooperation in the detoxification process could provide protection against the BaP toxicity of rare minnows at the early life stage. |