rs1045642(A;A)

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.