Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis

T. Dujic, K. Zhou, S. W. Yee, N. van Leeuwen, C. E. de Keyser, M. Javorský, S. Goswami, L. Zaharenko, M. M. Hougaard Christensen, M. Out, R. Tavendale, M. Kubo, M. M. Hedderson, A. A. van der Heijden, L. Klimčáková, V. Pirags, A. Kooy, K. Brøsen, J. Klovins, S. SemizI. Tkáč, B. H. Stricker, C. N.A. Palmer, L. M. 't Hart, K. M. Giacomini, E. R. Pearson

研究成果: Article

29 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)763-772
ページ数10
ジャーナルClinical Pharmacology and Therapeutics
101
発行部数6
DOI
出版物ステータスPublished - 01-06-2017

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Metformin
Meta-Analysis
Pharmacokinetics
Type 2 Diabetes Mellitus
Organic Cation Transporter 1
Genes
Genotype
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

これを引用

Dujic, T., Zhou, K., Yee, S. W., van Leeuwen, N., de Keyser, C. E., Javorský, M., ... Pearson, E. R. (2017). Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis. Clinical Pharmacology and Therapeutics, 101(6), 763-772. https://doi.org/10.1002/cpt.567
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. ; Klimčáková, L. ; Pirags, V. ; Kooy, A. ; Brøsen, K. ; Klovins, J. ; Semiz, S. ; Tkáč, I. ; Stricker, B. H. ; Palmer, C. N.A. ; 't Hart, L. M. ; Giacomini, K. M. ; Pearson, E. R. / Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin : A Metgen Meta-Analysis. :: Clinical Pharmacology and Therapeutics. 2017 ; 巻 101, 番号 6. pp. 763-772.
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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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Dujic, T, Zhou, K, Yee, SW, van Leeuwen, N, de Keyser, CE, Javorský, M, Goswami, S, Zaharenko, L, Hougaard Christensen, MM, Out, M, Tavendale, R, Kubo, M, Hedderson, MM, van der Heijden, AA, Klimčáková, L, Pirags, V, Kooy, A, Brøsen, K, Klovins, J, Semiz, S, Tkáč, I, Stricker, BH, Palmer, CNA, 't Hart, LM, Giacomini, KM & Pearson, ER 2017, 'Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis', Clinical Pharmacology and Therapeutics, 巻. 101, 番号 6, pp. 763-772. https://doi.org/10.1002/cpt.567

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.; Klimčáková, L.; Pirags, V.; Kooy, A.; Brøsen, K.; Klovins, J.; Semiz, S.; Tkáč, I.; Stricker, B. H.; Palmer, C. N.A.; 't Hart, L. M.; Giacomini, K. M.; Pearson, E. R.

:: Clinical Pharmacology and Therapeutics, 巻 101, 番号 6, 01.06.2017, p. 763-772.

研究成果: Article

TY - JOUR

T1 - Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin

T2 - A Metgen Meta-Analysis

AU - Dujic, T.

AU - Zhou, K.

AU - Yee, S. W.

AU - van Leeuwen, N.

AU - de Keyser, C. E.

AU - Javorský, M.

AU - Goswami, S.

AU - Zaharenko, L.

AU - Hougaard Christensen, M. M.

AU - Out, M.

AU - Tavendale, R.

AU - Kubo, M.

AU - Hedderson, M. M.

AU - van der Heijden, A. A.

AU - Klimčáková, L.

AU - Pirags, V.

AU - Kooy, A.

AU - Brøsen, K.

AU - Klovins, J.

AU - Semiz, S.

AU - Tkáč, I.

AU - Stricker, B. H.

AU - Palmer, C. N.A.

AU - 't Hart, L. M.

AU - Giacomini, K. M.

AU - Pearson, E. R.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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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