rs1045642

rs1045642, also known as C3435T, is a SNP located in the ABCB1 gene. It is often studied in conjunction with rs2032582. C3435T has been mentioned by: * A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity (for example, to verapamil) * (R)-lansoprazole (Prevacid) concentrations are significantly increased in CYP2C19 extensive metabolizers with ABCB1 C3435T C allele. * In a Korean population, plasma concentrations of fexofenadine (Allegra) were 17% lower in 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects compared to 2677GG/3435CC subjects. * In contrast, in this study no association was observed between the C3435T polymorphism and fexofenadine plasma or urine concentrations in a German Caucasian population. * A meta-analysis including 9 case-control studies (totaling ~2,500 patients) found no association between rs1045642 and epilepsy risk A study of 98 methadone-maintaining patients concluded that the higher (>150 mg/day) and lower ( T and 3435C>T polymorphism and sporadic colorectal cancer among Bulgarian patients. ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder. Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group. Multiplexed genotyping of ABC transporter polymorphisms with the Bioplex suspension array. A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia: a report from the Children's Oncology Group. Association of ABCB1 genetic variants with renal function in Africans and in Caucasians. Genotyping panel for assessing response to cancer chemotherapy. Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues. Bidirectional translational research: Progress in understanding addictive diseases. The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis. No association of ABCB1 polymorphisms with drug-refractory epilepsy in a north Indian population. Germline genetic variations in drug action pathways predict clinical outcomes in advanced lung cancer treated with platinum-based chemotherapy. Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994. Opiate and cocaine addiction: from bench to clinic and back to the bench. Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate. Steroid biosynthesis and renal excretion in human essential hypertension: association with blood pressure and endogenous ouabain. Genetic determinants of target and novelty-related event-related potentials in the auditory oddball response. ABCB1 (MDR1) rs1045642 is associated with increased overall survival in plasma cell myeloma. No significant effect of ABCB1 haplotypes on the pharmacokinetics of fluvastatin, pravastatin, lovastatin, and rosuvastatin. Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant. Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study. Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part I. Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part II. Explaining variability in ciclosporin exposure in adult kidney transplant recipients. Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. ABCB1/MDR1 gene polymorphisms as a prognostic factor in colorectal cancer. ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment. Cytochrome P450 genetic polymorphisms influence the serum concentration of calcineurin inhibitors in allogeneic hematopoietic SCT recipients. Pharmacogenetics of antidepressant response. Correlation between genetic polymorphisms of the hOCT1 and MDR1 genes and the response to imatinib in patients newly diagnosed with chronic-phase chronic myeloid leukemia. Impact of ABCB1 C3435T polymorphism on lymph node regression in multimodality treatment of locally advanced esophageal cancer. Ultra-resistant schizophrenia is not associated with the multidrug-resistant transporter 1 (MDR1) gene rs1045642 variant. The effects of CYP3A4, CYP3A5, ABCB1, ABCC2, ABCG2 and SLCO1B3 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of docetaxel in nasopharyngeal carcinoma patients. Expression of CYP3A5 and P-glycoprotein in renal allografts with histological signs of calcineurin inhibitor nephrotoxicity. Polymorphisms of the MDR1 and MIF genes in children with nephrotic syndrome. The clinical impact of ABCB1 polymorphisms on the treatment of psychiatric diseases. Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy. Polymorphisms in genes that regulate cyclosporine metabolism affect cyclosporine blood levels and clinical outcomes in patients who receive allogeneic hematopoietic stem cell transplantation. Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: a Gynecologic Oncology Group study. ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib. Variants in ABCB1, TGFB1, and XRCC1 genes and susceptibility to viral hepatitis A infection in Mexican Americans. Influence of genomic ancestry on the distribution of SLCO1B1, SLCO1B3 and ABCB1 gene polymorphisms among Brazilians. Association between the functional polymorphism (C3435T) of the gene encoding P-glycoprotein (ABCB1) and major depressive disorder in the Japanese population. MDR1 C3435T polymorphism and cancer risk: a meta-analysis based on 39 case-control studies. A comprehensive investigation on common polymorphisms in the MDR1/ABCB1 transporter gene and susceptibility to colorectal cancer. Neither P-gp SNP variants, P-gp expression nor functional P-gp activity predicts MDR in a preliminary study of plasma cell myeloma. PharmGKB summary: phenytoin pathway.

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Association between ABCB1 C3435T polymorphism and increased risk of cannabis dependence. (2009). ncbi.nlm.nih.gov Patients with cannabis dependence (n=40) had a significantly higher 3435C allele frequency (62.5% versus 43.8% respectively, P=0.017) and CC genotype (50% versus 20%, P=0.005, OR=4.00 [1.50-10.60]). The CC genotype was independently associated with cannabis dependence. This is the first time a significant specific genetic marker has been shown in cannabis dependence. ABCB1 polymorphisms may alter Delta9THC distribution, its psychoactive effects and individual vulnerability to dependence.

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This is the homozygous variant of C3435T, on the gene encoding P-glycoprotein (called MDR1 or ABCB1). P-glycoprotein is a protein involved in pumping foreign substances out of cells. It mainly affects areas of the body that have a barrier or excretory function: blood-tissue barrier, the gastrointestinal tract, liver and kidney. Poor functioning of this cellular defense mechanism can affect elimination of carcinogens and movement of drugs in the system. == Drug Treatment Response & Toxicity == ABCB1 polymorphism as prognostic factor in breast cancer patients treated with docetaxel and doxorubicin neoadjuvant chemotherapy. (2014). Among 216 patients, those with the 3435TT genotype had a longer overall survival than CC/CT. ABCB1 3435TT genotype had a higher blood concentration than CC/CT for docetaxel. These higher values in the C3435TT were associated with increased toxicities of neutropenia (low count of a type of white blood cell) and diarrhea. This study showed that the genetic polymorphism of ABCB1 C3435T might be associated with a longer overall survival. Our results also suggest that the prediction of docetaxel toxicity might be possible for C3435T polymorphism. Effect of polymorphisms within methotrexate pathway genes on methotrexate toxicity and plasma levels in adults with hematological malignancies. (2014). ncbi.nlm.nih.gov Individuals respond differently to the cancer drug methotrexate (MTX) and experience differences in toxicity. The authors evaluated the impact of SNPs within the MTX pathway genes on MTX-induced toxicity and MTX plasma levels at 48 hours following treatment in Asian adults with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Patients with MTHFR C677T and ABCB1 C3435T polymorphisms appear to have significantly higher MTX plasma concentrations (p T polymorphism is associated with increased cancer risk; however, when stratified by cancer type, the only cancer showing a statistically significant increase was acute lymphoblastic leukemia (ALL). MDR1 (C3435T) polymorphism: relation to the risk of breast cancer and therapeutic outcome. (2010).nature.com Statistically significant higher C3435T allele frequency found in breast cancer patients (n=221) than in controls (n=113), implying slight increase in risk. Poorer therapeutic outcome after chemotherapy and shorter time to progression after anthracycline-based chemotherapy was observed in TT homozygotes. == Alzheimer's Disease == Blood–brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients: effect of polymorphisms in the ABCB1 gene.(2012). ncbi.nlm.nih.gov Single-nucleotide polymorphisms in ... C3435T are related to changes in blood-brain barrier P-glycoprotein function in Alzheimer's patients, but not in healthy controls. In Alzheimer's patients, genetic variations in ABCB1 might contribute to the progression of amyloid-beta deposition in the brain. == Major Depressive Disorder == Association between the functional polymorphism (C3435T) of the gene encoding P-glycoprotein (ABCB1) and major depressive disorder in the Japanese population. (2012). ncbi.nlm.nih.gov Results suggest that the T3435 allele or carrying two copies of this allele confers slightly increased susceptibility to MDD in the Japanese population.