Adenosine Triphosphate-binding Cassette Subfamily B Member 1 Research Articles

Gene Polymorphism in Five Target Genes of Immunosuppressive Therapy and Risk of Development of Preeclampsia.

Pregnancy can be considered as an allogeneic transplant and preeclampsia can be seen as a failure of the acceptance mechanisms of this transplant as occurs in acute organ transplant rejection. Some genetic polymorphisms may be involved in its pathogenesis. Since the kidney is one of the organs mainly involved in preeclampsia, our study attempted to determine the frequencies of single nucleotide polymorphisms of DNA (SNP) in 3 genes (adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1)/multi drug reactivity 1 (MDR1) gene, interleukin 10 gene and tumor necrosis factor α gene) which are targets of immunosuppressive therapies and related to acute renal rejection. The study was an observational, monocentric, case-control study. We enrolled 20 women with severe preeclampsia and 10 women age-matched with regular pregnancy. Continuous variables were compared by the Student’s t-test for independent variables or using the Mann-Whitney test depending on their distribution. We used Fisher test to compare categorical variables between cases and controls, while we used logistic regression model to evaluate which risk factor was associated with preeclampsia. Although there was no statistically significant difference between the two groups, we found different percentages of two of the polymorphisms considered (rs1045642 and rs2032582 in the gene ABCB1). Despite these results, our work may be helpful for future research to better understand the pathogenesis of preeclampsia.

CYP3A5 polymorphisms and their effects on tacrolimus exposure in an ethnically diverse South African renal transplant population.

Tacrolimus forms the cornerstone for immunosuppression in solid-organ transplantation. It has a narrow therapeutic window with wide inter- and intra-patient variability (IPV). Cytochrome P-450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A>G is the most frequently studied polymorphism in the CYP3A5 gene. The rs776746A>G (i.e. CYP3A5*3) single-nucleotide polymorphism in CYP3A5 alters tacrolimus predose trough concentration (C0) and may also affect IPV, which may lead to immune- and/or drug-mediated allograft injury. CYP3A5*3 may result in absent (*3/*3), partial (*1/*3) or normal (*1/*1) CYP3A5 expression. The effect of CYP3A5*3 on tacrolimus exposure and variability has not been examined in South African (SA) transplant recipients. To determine the frequencies and effect of CYP3A5 and adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) polymorphisms on tacrolimus C0/dose ratios in different ethnic groups attending a tertiary renal transplant clinic in SA, and other factors that may explain inter- and IPV in tacrolimus C0. All consenting stable renal transplant recipients on tacrolimus at the Livingstone Hospital Renal Unit in Port Elizabeth, SA, were included. Tacrolimus concentrations were obtained using a microparticle enzyme immunoassay method (ARCHITECT analyser, Abbott Laboratories). Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5*3 and *6 allelic variants. There were 43 participants (35% black African, 44% mixed ancestry and 21% white), with a mean age of 44.5 years, median duration post-transplant of 47 months and median (interquartile range) creatinine and estimated glomerular filtration rate levels of 118(92- 140) µmol/L and 62 (49 - 76) mL/min at study inclusion. The mean tacrolimus C0 in the study was 6.7 ng/mL, with no difference across the different ethnic groups. However, the mean total daily dose of tacrolimus required was 9.1 mg (0.12 mg/kg), 7.2 mg (0.09 mg/kg) and 4.3 mg (0.06 mg/kg) in black, mixed-ancestry and white patients, respectively (p=0.017). The frequencies for CYP3A5 expressors (i.e. CYP3A5*1/*1 + CYP3A5*1/*3 genotypes) were 72%, 100%, 76% and 12% for all patients combined and black, mixed-ancestry and white patients, respectively. The frequencies for CYP3A5 non-expressors (i.e. CYP3A5*3/*3 genotypes) were 0%, 24% and 88% among the black, mixed-ancestry and white patients, respectively. None of the patients carried the CYP3A5*6 allele. CYP3A5*1/*1 and CYP3A5*1/*3 genotype carriers required a two-fold increase in dose compared with the non-expressor genotype carriers, CYP3A5*3/*3 (p<0.05). CYP3A5*3/*3 carriers also demonstrated higher IPV than CYP3A5*1/*1 and *1/*3 carriers (18.1% v. 14.2%; p=0.125). Compared with global transplant populations, SA renal transplant recipients demonstrated a very high rate of CYP3A5 expression, with a significant impact on tacrolimus pharmacokinetics. Genetic variation in CYP3A5 expression affects tacrolimus dosing requirements, and knowing the CYP3A5 genotype of transplant patients may allow better dose prediction compared with current standard dosing recommendations in a multi-ethnic population. Overall, black African patients required higher doses of tacrolimus than their white counterparts. While further prospective studies are needed to better evaluate dosing algorithms, it would appear that the starting dose of tacrolimus should be higher in black and mixed-race patients.

Acute rejection in kidney transplantation and the evaluation of associated polymorphisms (SNPs): the importance of sample size.

Background Acute rejection (AR) is one of the most frequent complications after kidney transplantation (KT). Scientific evidence reports that some single-nucleotide polymorphisms (SNPs) located in genes involved in the immune response and in the pharmacokinetics and pharmacodynamics of immunosuppressive drugs are associated with rejection in renal transplant patients. The aim of this study was to evaluate some SNPs located in six genes: interleukin-10 (IL-10), tumor necrosis factor (TNF), adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), uridine diphosphate glucuronosyltransferase family 1 member A9 (UGT1A9), inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2. Methods We enrolled cases with at least one AR after KT and two groups of controls: patients without any AR after KT and healthy blood donors. Genetic analysis on DNA was performed. The heterozygosity (HET) was determined and the Hardy-Weinberg equilibrium (HWE) test was performed for each SNP. The sample size was calculated using the QUANTO program and the genetic associations were calculated using the SAS program (SAS Institute Inc., Cary, NC, USA). Results In our previous preliminary study (sample size was not reached for cases), the results showed that patients with the C allele in the SNP rs1045642 and the A allele in the SNP rs2032582 of the ABCB1 gene had more frequent AR. In contrast, with the achievement of sample size, the trend of the previous data was not confirmed. Conclusions Our study highlights a fundamental aspect of scientific research that is generally presumed, i.e. the sample size of groups enrolled for a scientific study. We believe that our study will make a significant contribution to the scientific community in the discussion of the importance of the analysis and the achievement of sample size to evaluate the associations between SNPs and the studied event.

Polymorphisms in CYP1A2, CYP2C9 and ABCB1 affect agomelatine pharmacokinetics.

Agomelatine is an agonist of the melatoninergic receptors used for the treatment of depression. Our aim was to evaluate the effect of genetic polymorphisms in metabolising enzymes and the P-glycoprotein transporter on agomelatine pharmacokinetics and pharmacodynamics. Twenty-eight healthy volunteers receiving a single 25 mg oral dose of agomelatine, were genotyped for nine polymorphisms in cytochrome P450 enzymes ( CYP1A2, CYP2C9 and CYP2C19) and adenosine triphosphate-binding cassette subfamily B member 1 ( ABCB1), by real-time polymerase chain reaction . Agomelatine concentrations were measured by high performance liquid chromatography coupled to a tandem mass spectrometry detector. We calculated a CYP1A2 activity score that was directly correlated with agomelatine pharmacokinetics. Individuals with a decreased enzyme activity (*1C carriers) had a lower clearance and accumulated higher concentrations of agomelatine. In contrast, individuals with a high CYP1A2 inducibility (*1F or *1B carriers) showed an extensive clearance and lower agomelatine concentrations. The apparently marked differences between races were due to the different CYP1A2 genotype distribution. CYP2C9 intermediate/poor metabolisers showed a higher area under the concentration-time curve and maximum concentration. ABCB1 G2677T/A polymorphism affected the time to reach maximum concentration, as subjects carrying A/A+A/T genotypes showed higher values. No association was found for CYP2C19 phenotype. Agomelatine did not produce any change in blood pressure, heart rate or QT interval. CYP1A2 polymorphisms affect agomelatine pharmacokinetics. CYP1A2 phenotype inferred from the genotyping of CYP1A2*1C, *1F and *1B alleles might be a potential predictor of agomelatine exposure. ABCB1 G2677T/A could affect agomelatine absorption, as subjects with A/A+A/T genotypes had lower agomelatine concentration and they take more time to reach the maximum concentration.

Involvement of adenosine triphosphate-binding cassette subfamily B member 1 in the augmentation of triacylglycerol excretion by Propionibacterium acnes in differentiated hamster sebocytes.

An onset of acne, a common inflammatory skin disease, is associated with excess sebum production and secretion in sebaceous glands. Because Propionibacterium acnes has been reported to augment intracellular sebum accumulation in sebaceous glands in hamsters, it remains unclear whether P. acnes influences sebum secretion from differentiated sebocytes. Both P. acnes culture media (Acnes73-CM) and formalin-killed P. acnes (F-Acnes73) dose-dependently increased the extracellular levels of triacylglycerol (TG), a major sebum component, and Rhodamine 123, a substrate of adenosine triphosphate-binding cassette (ABC) transporter, from differentiated hamster sebocytes (DHS). In addition, the gene expression of the ABC subfamily B member 1 (ABCB1) was dose-dependently augmented by adding Acnes73-CM and F-Acnes73 into DHS. Furthermore, the F-Acnes73-induced increase of TG excretion was suppressed by PSC833, a selective ABCB1 inhibitor. On the other hand, peptidoglycan (PGN), which is a Toll-like receptor 2 (TLR2) ligand in P. acnes, increased extracellular TG levels, transporter activity and ABCB1 mRNA expression in DHS. The PGN-augmented TG excretion was suppressed by PSC833. Thus, these results provide novel evidence that P. acnes facilitates sebum secretion due to the activation of ABCB1 concomitantly with the increased ABCB1 expression, which may result from the activation of the TLR2 pathway in DHS. Therefore, the ABCB1 inhibitor is likely to become a candidate as a possible therapeutic for the treatment of acne.

Drug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patients: A hospital-based observational study.

Chemotherapy-induced neutropenia (CIN) is one of the major adverse events that necessitate chemotherapy dose reduction. This study aimed to evaluate the association between grade 4 neutropenia and genetic polymorphisms in breast cancer patients. In this genetic polymorphism association study, peripheral blood samples from 100 consecutive breast cancer outpatients, between August 2012 and September 2014, treated with doxorubicin and cyclophosphamide (AC) combination chemotherapy were genotyped for polymorphisms in adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), cytochrome P450 (CYP) enzyme-coding genes (CYP2B6 and CYP3A5), glutathione S-transferase (GST), and excision repair cross-complementing 1 (ERCC1). Associations between grade 4 neutropenia and genotypes as well as risk factors were examined using multivariate logistic regression. From 100 patients, 32.0% had grade 4 neutropenia. Multivariate logistic regression analysis revealed that ERCC1 118C > T (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.22-9.69; P = 0.020), CYP2B6*6 (OR, 4.51; 95% CI, 1.21-16.95; P = 0.025), body mass index (BMI) (OR, 6.94; 95% CI, 1.15-41.67; P = 0.035), and baseline white blood cell (WBC) count (OR, 2.99; 95% CI, 1.06-8.40; P = 0.038) were significant predictors of grade 4 neutropenia. ERCC1 and CYP2B6 gene polymorphisms were associated with the extent of grade 4 neutropenia in patients receiving AC chemotherapy. In addition to previously known risk factors, BMI and WBC counts, ERCC1 and CYP2B6 gene polymorphisms were also identified as independent strong predictors of grade 4 neutropenia.

Pharmacokinetics of a Once-Daily Dose of Tacrolimus Early After Liver Transplantation: With Special Reference to CYP3A5 and ABCB1 Single Nucleotide Polymorphisms.

BACKGROUND The aim of the present study was to investigate the pharmacokinetics of the once-daily tacrolimus formulation (QD form) in relation to polymorphisms of the donor cytochrome P450 family 3 sub-family A polypeptide 5 (CYP3A5) gene and recipient adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1) gene. MATERIAL AND METHODS A total of 80 consecutive living-donor liver transplant (LDLT) recipients were started on the QD form of tacrolimus (day 1), and 60 patients were completely followed for 7 days early after liver transplantation in order to evaluate the pharmacokinetics. RESULTS The concentration/dose (C/D) ratio in recipients with the donor CYP3A5 *1 allele was significantly lower throughout the observation period compared with those with the CYP3A5 genotype *3/*3 (p<0.001), while no effect of single-nucleotide polymorphisms (SNPs) of ABCB1 was observed. The administered doses required to achieve the target trough level were significantly higher on day 7 than on day 1 among all groups, regardless of the differences in the SNPs, especially among those with donor CYP3A5 *1 allele. The tacrolimus concentration was kept within the targeted level all through the study regardless of SNPs. CONCLUSIONS The donor CYP3A5 *1 allele correlated with the lower C/D ratio after administration of the QD form, and higher doses of QD-form tacrolimus and careful monitoring for the trough level should be considered, especially in recipients with the donor CYP3A5 *1 allele.

Relationship between ABCB1 gene polymorphisms and severe neutropenia in patients with breast cancer treated with doxorubicin/cyclophosphamide chemotherapy

Chemotherapy-induced neutropenia is one of the major adverse events which results in the reduction of chemotherapy. Doxorubicin is a substrate of the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) transporter; reportedly, ABCB1 polymorphisms influence doxorubicin pharmacokinetics. We evaluated the association between chemotherapy-induced neutropenia and ABCB1 polymorphisms in patients with breast cancer. We investigated 141 patients with breast cancer treated with doxorubicin and cyclophosphamide (AC) chemotherapy. Peripheral blood samples obtained from patients were genotyped for the ABCB1 2677G>T/A and 3435C>T polymorphisms. The genotypes were then investigated for their association with grade 3 or greater neutropenia, and further their risk factors were examined using a multivariate logistic regression. The proportion of patients with grade 3 or greater neutropenia was 85.7% in the homozygous variant group, and 80% and 58.6% in the heterozygous variant and GG genotype groups, respectively (p = 0.021). The multivariate logistic regression analysis revealed that the ABCB1 2677G>T/A polymorphism was a strong predictor of grade 3 or greater neutropenia (odds ratio: 3.76; 95% confidence interval: 1.44–9.81; p = 0.007). ABCB1 polymorphisms may influence the extent of chemotherapy-induced neutropenia in AC combination-treated patients with breast cancer.

Impact of the ABCB1 Gene Polymorphism on Plasma 9-Hydroxyrisperidone and Active Moiety Levels in Japanese Patients With Schizophrenia

9-Hydroxyrisperidone (9-OH-RIS) is an active metabolite of the antipsychotic drug risperidone (RIS). The total active moiety level, in other words the sum of the RIS and 9-OH-RIS serum levels, may be important for estimating the clinical effects of RIS treatment. However, there have been no consistent results reported regarding the relationship between cytochrome P450 (CYP) 2D6 or adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) variant alleles and 9-OH-RIS or total active moiety plasma levels. Seventy-four Japanese patients treated with RIS were examined in the present study. Steady-state plasma RIS and 9-OH-RIS were measured. The CYP2D6*5, CYP2D6*10, ABCB1 3435C>T, and ABCB1 2677G>T/A genotypes were detected. Multiple regression analysis showed that the dose-corrected plasma RIS levels were significantly correlated with the number of CYP2D6 variant alleles and ABCB1 3435C>T genotypes, whereas the 9-OH-RIS and total active moiety levels were significantly correlated with the ABCB1 3435C>T genotypes and with age. On the other hand, the ABCB1 2677G>T/A genotypes did not affect plasma RIS, 9-OH-RIS, or total active moiety levels. The ABCB1 3435C>T genetic polymorphism may predict plasma 9-OH-RIS and total active moiety levels.

Correlation between Imatinib Trough Concentration and Efficacy in Chinese Chronic Myelocytic Leukemia Patients

Background: Trough imatinib plasma concentration, intracellular drug levels and expression of drug transporters can be indicative of clinical responses in chronic myelocytic leukemia (CML) patients receiving imatinib. We aimed to determine plasma imatinib concentration, intracellular imatinib concentration, human organic cation transporter 1 (hOCT1) and adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) mRNA expression in bone marrow cells of CML patients in order to evaluate the potential usefulness of these measures as markers of imatinib efficacy and understand their clinical relationships. Methods: Eighty-four CML patients receiving imatinib treatment were included in this study. Imatinib trough concentration was determined by high-performance liquid chromatography-tandem mass spectrometry. Real-time quantitative PCR with a TaqMan probe was used to assess hOCT1 and ABCB1 mRNA expression in bone marrow cells. All patients were divided into the major molecular response (MMR), complete cytogenetic response (CCyR), partial cytogenetic response (PCyR) or drug-resistant groups according to their response. Results: The plasma imatinib trough concentration was significantly higher in the MMR group than in the PCyR (p = 0.002) or drug-resistant groups (p = 0.011). The plasma imatinib trough concentration was also significantly higher in the CCyR group than in the PCyR group (p = 0.027). There were no significant differences between the CCyR and MMR groups with regard to the plasma imatinib trough concentration (p = 0.136). The intracellular imatinib concentration in bone marrow cells was significantly higher in the CCyR group compared to the drug-resistant or PCyR groups (p = 0.013). The hOCT1 mRNA expression in bone marrow cells was significantly higher in the CCyR group than in the drug-resistant or PCyR groups (p = 0.036). The ABCB1 mRNA expression in bone marrow cells was significantly higher in the drug-resistant group than in the CCyR or PCyR groups (p = 0.013). Plasma imatinib trough concentration was positively correlated with α₁-acid glycoprotein (r = 0.443, p < 0.001) or dose (r = 0.422, p < 0.001). Conclusions: Clinical responses in CML patients are correlated with both the plasma trough concentrations and intracellular levels of imatinib.

Investigation of ABCB1 gene polymorphism with colchicine response in Behçet’s disease

Colchicine is commonly used in the treatment of Behçet's disease. However, some patients are unresponsive to colchicine treatment. Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) transports colchicine out of cells. We investigated a possible association of C3435T polymorphism of the ABCB1 (MDR1) gene with colchicine response in patients with Behçet's disease. We randomly selected 97 patients with Behçet's disease, examined ABCB1 (MDR1) gene C3435T polymorphisms, and evaluated patient responses to colchicine. Forty-three patients were colchicine responsive, while the remaining 54 patients were unresponsive. No significant difference was found between genotypic and allelic frequencies of the ABCB1 C3435T polymorphisms in patients with Behçet's disease and healthy volunteers. Also, there was no significant difference among responsive and nonresponsive patients. We concluded that ABCB1 C3435T polymorphism is not associated with a colchicine response in patients with Behçet's disease.

CYP3A5 *1 Allele: Impacts on Early Acute Rejection and Graft Function in Tacrolimus-Based Renal Transplant Recipients

Tacrolimus is a major immunosuppressant, which has a narrow therapeutic range and wide interindividual variation. The effects of genetic polymorphisms of cytochrome P450 3A (CYP3A) 5 and Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) genes on the achievement of target tacrolimus trough levels and clinical outcomes in renal transplants were evaluated. A total of 62 patients participated in this prospective study. After an initial fixed oral dose (0.08 mg/kg two times per day), tacrolimus doses were adjusted to a target range based on daily measurement of blood trough concentration. Every patient underwent 10-day scheduled biopsy. Both the patients and investigators were blinded for the genetic polymorphisms. Those subjects expressing CYP3A5 (n=29) evidenced significantly lower tacrolimus trough levels between days 1 and 5 after transplantation, when compared with nonexpressers (n=33). Significantly higher overall incidences of early T-cell-mediated rejection (TCR) of at least Banff grade 1 in severity (P=0.017), including clinical rejection within 10 days and subclinical rejection in biopsies at postoperative day 10 were detected in CYP3A5 expressers. The severity of TCR according to Banff '07 classification was associated with CYP3A5 genotypes (P=0.012). Moreover, multivariate analysis identified CYP3A5 expression as an independent risk factor for TCR (odds ratio: 2.79; P=0.043). Significantly lower estimated glomerular filtration rates until 1 month and numerically lower estimated glomerular filtration rates by 12 months were noted in the CYP3A5 expressers. The genetic polymorphisms of the ABCB1 genes exerted no significant effects. We confirmed the significant effects of CYP3A5 polymorphism on the achievement of target tacrolimus trough levels and the development of acute rejection in early period after transplantation and consequent renal allograft function.

Association of ABCB1 polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting

We investigated whether the 2677G>T/A and 3435C>T polymorphisms of adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) affect the efficacy of ondansetron to prevent postoperative nausea and vomiting. One hundred and ninety-eight patients undergoing general anaesthesia were enrolled. Thirty minutes before the end of surgery, 0.1 mg.kg⁻¹ ondansetron was administered intravenously. The incidence of postoperative nausea and vomiting was compared between genotypes in the 2677G>T/A and 3435C>T polymorphisms of ABCB1. The incidence of postoperative nausea and vomiting was lower in patients with the 2677TT genotype (TT vs Non-TT = 25.9% vs 53.0%, p = 0.01) and 3435TT genotype (CC + CT vs TT = 52.6% vs 21.7%, p = 0.01) during the first 2 h after surgery. There were no significant differences in the incidence of postoperative nausea and vomiting between the different genotype groupings during period between 2 and 24 h after surgery. In conclusion, ABCB1 genotypes may be a clinical predictor of responsiveness for ondansetron.

Therapeutic Drug Monitoring and Clinical Outcomes in Epileptic Egyptian Patients: A Gene Polymorphism Perspective Study

This work was performed to explore the effect of polymorphism in multidrug resistant genes on plasma phenytoin levels and patient outcome to evaluate its involvement in drug resistance and toxicity, which is usually associated with antiepileptic drugs. Therefore, we genotyped the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) in 100 patients suffering from partial or generalized tonic-clonic seizures and receiving phenytoin and 50 healthy control subjects. Steady state plasma phenytoin levels were also determined in the epileptic patients. Patients were evaluated after 3 and 6 months and were classified either as drug resistant patients or responsive patients. Results revealed 37 patients with drug responsive epilepsy and 63 patients with drug resistant epilepsy. Genotyping of our patients and control subjects revealed a genotype distribution of CC, CT, TT: 55.50%, 38.00%, 6.50% for drug resistant patients, CC, CT, TT: 13.50%, 46.00%, 40.50% for drug responsive patients, and CC, CT, TT: 24.00%, 48.00%, 28.00% for the control subjects. Patients with drug-resistant epilepsy were more likely to have the CC than the TT genotype compared with either responsive patients (P < 0.0001) or control subjects (P < 0.0001). The C polymorphism was over-represented among patients with drug-resistant epilepsy as compared with either those with drug-responsive epilepsy (P < 0.001) or control subjects (P < 0.001). Of the total 100 epileptic patients, 13 patients had their plasma phenytoin levels exceeding the maximum safe concentration. These 13 patients were more likely to have TT genotype than the CC genotype compared with the remainder of patients who had their plasma phenytoin levels at 20 microg/mL or less. Responsive patients showed no deviation from the control group regarding the genotype (P > 0.05) or allele frequency (P > 0.05). In conclusion, because most of the antiepileptic drugs are multidrug resistant gene substrates, the ABCB1 is thus an important candidate gene for potentially influencing the response to antiepileptic drugs. Our findings suggest that using genotype data may make it possible to safely reduce the time required to reach an effective dose. Therefore, it is a priority to assess the utility of dose adjustment on the basis of genotype for these medicines that are substrates for this gene.

Association of the ABCB1 3435C&gt;T polymorphism with antiemetic efficacy of 5-hydroxytryptamine type 3 antagonists

Resistance to antiemetic treatment with 5-hydroxytryptamine type 3 (5-HT(3)) receptor antagonists is still a major problem resulting in patient discomfort and poor compliance to chemotherapy. We hypothesized that clinical resistance to 5-HT(3) antagonists is associated with the single-nucleotide polymorphism (3435C>T) in the gene that codes for the drug efflux transporter adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1). Patients with cancer (N = 216) treated with chemotherapeutic regimens composed of highly or moderately emetogenic agents were examined for their antiemetic responses to tropisetron, ondansetron, or granisetron. The efficacy of antiemetic treatment was documented by self-report charts for 5 days after chemotherapy. ABCB1 3435C>T genotype was determined to analyze its association with the antiemetic efficacy of 5-HT(3) antagonists. Within the first 24 hours of chemotherapy, the complete control rate of nausea and vomiting was higher in subjects with the ABCB1 TT genotype (n = 49) as compared with those with the CC (n = 60) or CT (n = 107) genotype (P = .044). The type of 5-HT(3) antagonists influenced the effect of genotype on antiemetic responses. The complete control rates were 92.9% in TT subjects (n = 14) in comparison to homozygote (47.6%, n = 21, P = .009) or heterozygote (56.1%, n = 41, P = .02) carriers of the 3435 C allele in granisetron-treated patients. However, during the delayed phase of chemotherapy, the complete control rates did not differ across genotypes. These results suggest that ABCB1 3435C>T polymorphism is associated with antiemetic treatment efficacy in patients with cancer treated with 5-HT(3) antagonists, particularly in granisetron-treated patients, during the short-term phase of chemotherapy.