Effect of 1022C>T and 1222A>G genetic polymorphisms of SLC22A1 gene on substrates binding to human organic cation transporter 1

Simple item page
dc.contributor.authorManvi, Akash Ashoken_US
dc.contributor.authorRodrigues, Elmer Cloveren_US
dc.contributor.authorAfreen, Munazzaen_US
dc.contributor.authorPadmapriyan, Samuel Gideon Georgeen_US
dc.date.accessioned2020-10-16T08:56:43Z
dc.date.available2020-10-16T08:56:43Z
dc.date.issued2020-09
dc.description.abstractHuman organic cation transporter 1 (hOCT1) is a transmembrane influx transporter protein encoded by the SLC22A1gene. hOCT1 plays a pivotal role in the hepatocellular and renal uptake of several xenobiotics and endogenoussubstrates. The human SLC22A1 gene is highly polymorphic. Non-synonymous single nucleotide polymorphisms(SNPs) of the human SLC22A1 gene tend to impair the transmembrane conductance of substrates by hOCT1. Herein,we describe the effect of 1022C>T and 1222A>G variations in the human SLC22A1 gene on hOCT1 structure andsubstrate binding. The three-dimensional (3D) structures of hOCT1 variants were ab initio models using the iTASSERserver, and drug-binding residues of the transmembrane domain were predicted using the Prankweb server. Substratebinding was analyzed by molecular docking using AutoDock 4.2.6. Amino acid residues, crucial for substrate bindingand transport, were altered in Met408Val and Pro341Leu variants and were suggestive of conformational changeinduced by 1022C>T and 1222A>G SNPs. Moreover, a statistically significant difference was observed betweenthe binding affinities of substrates to wild and mutant variants. Therefore, it is evident that 1022C>T and 1222A>Gnon-synonymous SNPs impair the drug uptake process of hOCT1, and hence patients with the former variants need tobe closely monitored for idiosyncratic adverse drug reactions or sub-therapeutic responses while being initiated intotherapy with hOCT1 substrates.en_US
dc.identifier.affiliationsDepartment of Pharmacy practice, Krupanidhi College of Pharmacy, Bengaluru, Karnataka, India.en_US
dc.identifier.citationManvi Akash Ashok, Rodrigues Elmer Clover, Afreen Munazza, Padmapriyan Samuel Gideon George. Effect of 1022C>T and 1222A>G genetic polymorphisms of SLC22A1 gene on substrates binding to human organic cation transporter 1. Journal of Applied Pharmaceutical Science. 2020 Sep; 2020 Sep: 072-081en_US
dc.identifier.issn2231-3354
dc.identifier.placeIndiaen_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/210665
dc.languageenen_US
dc.publisherOpen Science Publishers LLPen_US
dc.relation.issuenumber9en_US
dc.relation.volume10en_US
dc.source.urihttps://dx.doi.org//10.7324/JAPS.2020.10909en_US
dc.subjectOrganic cation transporteren_US
dc.subjectnon-synonymousen_US
dc.subjectpolymorphismen_US
dc.subjectdrug transporten_US
dc.titleEffect of 1022C>T and 1222A>G genetic polymorphisms of SLC22A1 gene on substrates binding to human organic cation transporter 1en_US
dc.typeJournal Articleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
japs2020v10n9p072.pdf
Size:
4.72 MB
Format:
Adobe Portable Document Format
Download
Collections
Journal of Applied Pharmaceutical Science (JAPS)