Relationship between genetic polymorphism of drug transporters and the efficacy of Rosuvastatin, atorvastatin and simvastatin in patients with hyperlipidemia

Background To determine the effect of genetic polymorphism of drug transporters on the efficacy of treatment with Rosuvastatin, Atorvastatin and Simvastatin in patients with hyperlipidemia. Methods The study consists of 180 patients, aged 40–75 years, with hyperlipidemia. All patients were divided into two equal groups: patients with different SLCO1B1 (521CC, 521CT and 521TT) and MDR1 (3435CC, 3435TC and 3435TT) genotypes. Each group was divided into rosuvastatin-treated, atorvastatin-treated and simvastatin-treated subgroups. The lipid-lowering effect of statins was assessed by tracing changes in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. Results The use of statins over a 4-month period led to substantial reductions in TC and LDL-C levels. The hypolipidemic effect of studied agents was seen in both groups. However, it was less pronounced in patients with 521CC genotype. No statistically significantly differences were found between carriers of 3435TT, 3435CT and 3435CC genotypes. Conclusions The lipid-lowering efficacy of rosuvastatin was higher compared to other two statins. Patients with SLCO1B1 521CC genotype are more likely to encounter a decrease in the hypolipidemic effect of statins. Such a risk should be considered when treating this category of patients. MDR1 polymorphism had no significant effect on statin efficacy.

Effects of MDR1 Gene Polymorphism on Efficacy and Hematotoxicity of Epirubicin-Based Regimen in Patients with Breast Cancer in Southwest China

Objective: To investigate the predictive value of multi-drug resistance gene (MDR1) polymorphism in the efficacy and hematological toxicity of chemotherapy regimen based on Epirubicin in patients with breast cancer in Southwest China. Methods: Patients who received Epirubicin-based chemotherapy were included, and polymorphism of C1236T, G2677T/A and C3435T were detected by time-of-flight mass spectrometry (TOF-MS). The correlation between different genotypes and chemotherapy efficacy and blood toxicity were evaluated. Results: A total of 102 patients were included, 44 of them were treated with neoadjuvant chemotherapy. There was no significant correlation between all genotypes and alleles of the three SNPs and the efficacy of neoadjuvant chemotherapy regimen containing Epirubicin in patients with breast cancer. There was a significant correlation between C3435T polymorphism and grade Ⅲ-Ⅳ leukopenia in patients with breast cancer, the incidence of grade Ⅲ-Ⅳ leukopenia in patients with C allele was significantly lower than that in patients with T allele. Conclusion: T allele of C3435T polymorphism may be a risk factor for grade Ⅲ-Ⅳ leukopenia in patients with breast cancer after chemotherapy.

Association between MDR1 gene polymorphism and clinical course of pediatric pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease with a complex pathogenesis. The polymorphism of the gene of multidrug resistance-1 (MDR1) has been associated with many diseases including PAH. Objective. In this study we aimed to investigate the relevance of the MDR1 polymorphism to pediatric PAH clinical course. Methods. A total of 40 pediatric patients with PAH (secondary to congenital heart defects or idiopathic) and 40 control subjects were enrolled. Patients with PAH were divided into 2 groups, according to their evolution: 28 patients who remained clinically stable at 12-months (non-worsening group) and 12 patients who presented clinical worsening at 12-months (worsening group). Genomic DNA was genotyped for MDR1 gene polymorphisms as follows: C1236T, G2677T and C3435T. Results. There were no significant differences between PAH children groups (clinical worsening and non-worsening) nor between PAH children and controls in terms of frequency distribution of the three studied genotypes or alleles. Conclusions. The MDR1 polymorphism could not be correlated with the clinical evolution of pediatric PAH patients in our study.

K13 Propeller Alleles, mdr1 Polymorphism, and Drug Effectiveness at Day 3 after Artemether-Lumefantrine Treatment for Plasmodium falciparum Malaria in Colombia, 2014-2015

ABSTRACT High treatment failure rates for Plasmodium falciparum malaria have been reported in Colombia for chloroquine, amodiaquine, and sulfadoxine-pyrimethamine. Artemisinin combination therapies were introduced in 2006 in Colombia, where artemether-lumefantrine (AL) is currently used to treat uncomplicated P. falciparum malaria. Artemisinin (ART) resistance was initially observed in Southeast Asia as an increased parasite clearance time, manifesting as a positive thick-blood smear on day 3 after treatment (D3 positivity). Recently, mutations in the propeller domain of the P. falciparum kelch13 gene (K13 propeller) have been associated with ART resistance. In this study, we surveyed AL effectiveness at D3 and molecular markers of drug resistance among 187 uncomplicated P. falciparum cases in 4 regions of Colombia from June 2014 to July 2015. We found that 3.2% (4/125) of patients showed D3 positivity, 100% (163/163) of isolates carried wild-type K13 propeller alleles, 12.9% (23/178) of isolates had multiple copies of the multidrug resistance 1 gene (mdr1), and 75.8% (113/149) of isolates harbored the double mutant NFSDD mdr1 haplotype (the underlining indicates mutant alleles). These data suggest that ART resistance is not currently suspected in Colombia but that monitoring for lumefantrine resistance and AL failures should continue.

Evaluation of C3435T MDR1 Gene Polymorphism in Adult Patient with Acute Lymphoblastic Leukemia

Background: P-glycoprotein (P-gp) is a transmembrane pump encoded by MDR1 gene. It contributes in protection of the cells against xenobiotic and toxic compounds. P-gp also contributes in multidrug resistance in acute lymphoblastic leukemia (ALL). Human MDR1 polymorphism include C to T exchange at position 3435, individuals with TT polymorphism have lower expression of P-gp than the others with CC genotypes. Accumulation of xenobiotics in the cells can cause some diseases like cancers.Materials and Methods: To evaluate MDR1C3435T gene polymorphism in adult patients with ALL, 54 patients and 96 healthy controls were involved in our survey. Genotyping of ALL patients and healthy controls was performed by Polymerase Chain Reaction – Restriction Fragment- Length Polymorphism (PCR-RFLP). Data analysis was done by SPSS software through T-test and Chi- Square. Results: No significant difference was found between C3435T MDR1 gene polymorphisms and incidence of ALL in adult patients. Also there was not any significant difference between T and C alleles and incidence of ALL. Conclusion: C3435T MDR1 polymorphism is not associated with the incidence of ALL in the population studied. Keyword: P-gp; C3435T; MDR1; ALL; polymorphism DOI: 10.3329/jom.v12i1.5541J Medicine 2011; 12 : 3-6