Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-Term response to metformin monotherapy in type 2 diabetes mellitus patients

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dc.contributor.authorZaharenko, Linda
dc.contributor.authorKalnina, Ineta
dc.contributor.authorGeldnere, Kristine
dc.contributor.authorKonrade, Ilze
dc.contributor.authorGrinberga, Solveiga
dc.contributor.authorŽidzik, Jozef
dc.contributor.authorJavorský, Martin
dc.contributor.authorLejnieks, Aivars
dc.contributor.authorNikitina-Zake, Liene
dc.contributor.authorFridmanis, Davids
dc.contributor.authorPeculis, Raitis
dc.contributor.authorRadovica-Spalvina, Ilze
dc.contributor.authorHartmane, Dace
dc.contributor.authorPugovics, Osvalds
dc.contributor.authorTká, Ivan
dc.contributor.authorKlimáková, Lucia
dc.contributor.authorPirags, Valdis
dc.contributor.authorKlovins, Janis
dc.contributor.institutionRīga Stradiņš University
dc.date.accessioned2021-05-27T11:05:01Z
dc.date.available2021-05-27T11:05:01Z
dc.date.issued2016-12
dc.descriptionPublisher Copyright: © 2016 The authors Published by Bioscientifica Ltd. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.
dc.description.abstractObjective(s): High variability in clinical response to metformin is often observed in type 2 diabetes (T2D) patients, and it highlights the need for identification of genetic components affecting the efficiency of metformin therapy. Aim of this observational study is to evaluate the role of tagSNPs (tagging single nucleotide polymorphisms) from genomic regions coding for six metformin transporter genes with respect to the short-Term efficiency. Design: 102 tagSNPs in 6 genes coding for metformin transporters were genotyped in the group of 102 T2D patients treated with metformin for 3 months. Methods: Most significant hits were analyzed in the group of 131 T2D patients from Slovakia. Pharmacokinetic study in 25 healthy nondiabetic volunteers was conducted to investigate the effects of identified polymorphisms. Results: In the discovery group of 102 patients, minor alleles of rs3119309, rs7757336 and rs2481030 were significantly nominally associated with metformin inefficiency (P = 1.9 × 106 to 8.1 × 106). Effects of rs2481030 and rs7757336 did not replicate in the group of 131 T2DM patients from Slovakia alone, whereas rs7757336 was significantly associated with a reduced metformin response in combined group. In pharmacokinetic study, group of individuals harboring risk alleles of rs7757336 and rs2481030 displayed significantly reduced AUC∞ of metformin in plasma. Conclusions: For the first time, we have identified an association between the lack of metformin response and SNPs rs3119309 and rs7757336 located in the 5 flanking region of the genes coding for Organic cation transporter 2 and rs2481030 located in the 5 flanking region of Organic cation transporter 3 that was supported by the results of a pharmacokinetic study on 25 healthy volunteers.en
dc.description.statusPeer reviewed
dc.format.extent10
dc.format.extent1002156
dc.identifier.citationZaharenko, L, Kalnina, I, Geldnere, K, Konrade, I, Grinberga, S, Židzik, J, Javorský, M, Lejnieks, A, Nikitina-Zake, L, Fridmanis, D, Peculis, R, Radovica-Spalvina, I, Hartmane, D, Pugovics, O, Tká, I, Klimáková, L, Pirags, V & Klovins, J 2016, 'Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-Term response to metformin monotherapy in type 2 diabetes mellitus patients', European Journal of Endocrinology, vol. 175, no. 6, pp. 531-540. https://doi.org/10.1530/EJE-16-0347
dc.identifier.doi10.1530/EJE-16-0347
dc.identifier.issn0804-4643
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/4552
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85000786627&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofEuropean Journal of Endocrinology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject3.2 Clinical medicine
dc.subject3.1 Basic medicine
dc.subject1.6 Biological sciences
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectEndocrinology, Diabetes and Metabolism
dc.subjectEndocrinology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleSingle nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-Term response to metformin monotherapy in type 2 diabetes mellitus patientsen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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