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Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.
Dujic, T; Zhou, K; Yee, S W; van Leeuwen, N; de Keyser, C E; Javorský, M; Goswami, S; Zaharenko, L; Hougaard Christensen, M M; Out, M; Tavendale, R; Kubo, M; Hedderson, M M; van der Heijden, A A; Klimcáková, L; Pirags, V; Kooy, A; Brøsen, K; Klovins, J; Semiz, S; Tkác, I; Stricker, B H; Palmer, Cna; 't Hart, L M; Giacomini, K M; Pearson, E R.
Afiliación
  • Dujic T; Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
  • Zhou K; Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK.
  • Yee SW; Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK.
  • van Leeuwen N; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
  • de Keyser CE; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
  • Javorský M; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Goswami S; Inspectorate of Healthcare, Utrecht, The Netherlands.
  • Zaharenko L; Department of Internal Medicine 4, Faculty of Medicine, Safárik University, Kosice, Slovakia.
  • Hougaard Christensen MM; Pasteur University Hospital, Kosice, Slovakia.
  • Out M; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
  • Tavendale R; Latvian Biomedical Research and Study Centre, Riga, Latvia.
  • Kubo M; Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
  • Hedderson MM; Treant Zorggroep, Location Bethesda, Hoogeveen, The Netherlands.
  • van der Heijden AA; Bethesda Diabetes Research Centre, Hoogeveen, The Netherlands.
  • Klimcáková L; Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK.
  • Pirags V; Core for Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Kooy A; Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
  • Brøsen K; Department of General Practice, EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
  • Klovins J; Department of Medical Biology, Faculty of Medicine, Safárik University, Kosice, Slovakia.
  • Semiz S; Latvian Biomedical Research and Study Centre, Riga, Latvia.
  • Tkác I; Treant Zorggroep, Location Bethesda, Hoogeveen, The Netherlands.
  • Stricker BH; Bethesda Diabetes Research Centre, Hoogeveen, The Netherlands.
  • Palmer C; Department of Public Health, Clinical Pharmacology and Pharmacy, University of Southern Denmark, Odense, Denmark.
  • 't Hart LM; Latvian Biomedical Research and Study Centre, Riga, Latvia.
  • Giacomini KM; Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
  • Pearson ER; International University of Sarajevo, Faculty of Engineering and Natural Sciences, Sarajevo, Bosnia and Herzegovina.
Clin Pharmacol Ther ; 101(6): 763-772, 2017 Jun.
Article en En | MEDLINE | ID: mdl-27859023
ABSTRACT
Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with inconsistent results. To clarify the significance of these variants in glycemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of the Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (organic cation transporter [OCT]1, OCT2, multidrug and toxin extrusion transporter [MATE]1, MATE2-K, and OCTN1) were analyzed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed a daily dose of metformin. Our results suggest that candidate transporter gene variants have little contribution to variability in glycemic response to metformin in T2D.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Proteínas de Transporte de Membrana / Glucemia / Polimorfismo de Nucleótido Simple / Diabetes Mellitus Tipo 2 / Variantes Farmacogenómicas / Hipoglucemiantes / Metformina Tipo de estudio: Diagnostic_studies / Systematic_reviews Idioma: En Revista: Clin Pharmacol Ther Año: 2017 Tipo del documento: Article
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Proteínas de Transporte de Membrana / Glucemia / Polimorfismo de Nucleótido Simple / Diabetes Mellitus Tipo 2 / Variantes Farmacogenómicas / Hipoglucemiantes / Metformina Tipo de estudio: Diagnostic_studies / Systematic_reviews Idioma: En Revista: Clin Pharmacol Ther Año: 2017 Tipo del documento: Article