Abstract
Multidrug resistance-associated proteins (MRP) 1 and 2 belong to the ABC (ATP-Binding Cassette) transporters. These transport proteins are involved in the removal of various drugs and xenobiotics, as well as in multiple physiological, pathological, and pharmacological processes. There is a strong correlation between different polymorphisms and their clinical implication in resistance to antiepileptic drugs, anticancer, and anti-infective agents. In our study, we evaluated exon regions of MRP1 (ABCC1)/MRP2 (ABCC2) in a Colombian cohort of healthy subjects to determine single nucleotide polymorphisms (SNPs) and to determine the allelic and genomic frequency. Results showed there are SNPs in our population that have been previously reported for both MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) and MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). Additionally, 13 new SNPs were identified. Evidence also shows a significant clinical correlation for polymorphisms rs3740066 and rs2273697 in the transport of multiple drugs, which suggests a genetic variability in regards to that reported in other populations.
Highlights
The ABC (ATP Binding Cassette or ABC transporters) transporters are formed by a large family of transmembrane proteins that bind ATP and use the energy of ATP hydrolysis to transport various components across the cell membrane [1]
New studies have revealed the role of MRP1 and MRP2 (Multidrug resistance-associated protein 2) in the transport of drugs and metabolites in multiple physiological, pathological, and pharmacological processes [5,6,7,8,9]
This is a descriptive study of allelic and genotypic frequencies of polymorphism in a group of exons of the MRP1/ABCC1 and MRP2/ABCC2 genes in a non-random sample population of healthy subjects with no medical history regarding the functions of the genes of interest
Summary
The ABC (ATP Binding Cassette or ABC transporters) transporters are formed by a large family of transmembrane proteins that bind ATP and use the energy of ATP hydrolysis to transport various components across the cell membrane [1]. The MRP1/ABCC1 (16p13.1) gene encodes a protein of about 1531 amino acids with a molecular weight of 180–190 KDa [10,11], which functions as a multi-specific transport of organic anions, with glutathione (oxidized), cysteinyl leukotrienes, and aflatoxin B1 activated as substrates. The transport of these conjugates helps the cell remove toxins and protect tissues from damage caused by the expression of mediators of the inflammatory response that controls vascular permeability and smoothens muscle contractions [5]. MRP1/ABCC1 can carry other drugs such as HIV antiretrovirals, and it is involved in the clinical response to treat this disease [14]
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