The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Genetic Variation in the Multidrug and Toxin Extrusion 1 Transporter Protein Influences the Glucose-Lowering Effect of Metformin in Patients With Diabetes: A Preliminary Study
Open accessAbstract
OBJECTIVE— Metformin, an oral glucose-lowering drug, is taken up in hepatocytes by the organic cation transporter (OCT) 1 and in renal epithelium by OCT2. In these cells, the multidrug and toxin extrusion (MATE) 1 protein, encoded by the SLC47A1 gene, is responsible for the excretion of metformin into the bile and urine, respectively. We studied the effect of single nucleotide polymorphisms (SNPs) in the SLC47A1 gene on the A1C-lowering effect of metformin. RESEARCH DESIGN AND METHODS— We identified all incident metformin users in the Rotterdam Study, a population-based cohort study. Associations between 12 tagging SNPs in the SLC47A1 gene and change in A1C level were analyzed. RESULTS— One hundred and sixteen incident metformin users were included in the study sample. The rs2289669 G>A SNP was significantly associated with metformin response. For the other SNPs, no associations were found. For each minor A allele at rs2289669, the A1C reduction was 0.30% (95% CI −0.51 to −0.10; P = 0.005) larger. After Bonferroni correction for multiple testing, the P value was 0.045. CONCLUSIONS— The rs2289669 G>A SNP is associated with a reduction in A1C level, consistent with a reduction in MATE1 transporter activity. These results suggest that the transporter MATE1, encoded by SLC47A1, may have an important role in the pharmacokinetics of metformin, although replication is necessary.
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The International HapMap Project
†The International HapMap Consortium, Genotyping centres: Baylor College of Medicine and ParAllele BioScience, Gibbs, R. A., Belmont, J. W., Hardenbol, P., Willis, T. D., Yu, F., Chinese HapMap Consortium, Yang, H., Ch'ang, L.-Y., et al. (2003) · Nature · doi:10.1038/nature02168 · Cited by 6,057
Kirpichnikov, D., McFarlane, S. I., & Sowers, J. R. (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-137-1-200207020-00009 · Cited by 1,084
Mechanism by which metformin reduces glucose production in type 2 diabetes.
Hundal, R. S., Krssak, M., Dufour, S., Laurent, D., Lebon, V, Chandramouli, V, Inzucchi, S. E., Schumann, W. C., Petersen, K. F., Landau, B. R., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.12.2063 · Cited by 1,052
Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin
Wang, D.-S., Jonker, J. W., Kato, Y., Kusuhara, H., Schinkel, A. H., & Sugiyama, Y. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.034140 · Cited by 441
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Metformin: from mechanisms of action to therapies
Foretz, M., Guigas, B., Bertrand, L., Pollak, M., & Viollet, B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.09.018 · Cited by 1,501
Clinical pharmacokinetics of metformin
Graham, G. G., Punt, J., Arora, M., Day, R. O., Doogue, M. P., Duong, J. K., Furlong, T. J., Greenfield, J. R., Greenup, L. C., Kirkpatrick, C. M., et al. (2011) · Clinical Pharmacokinetics · doi:10.2165/11534750-000000000-00000 · Cited by 1,318
Metformin pathways: pharmacokinetics and pharmacodynamics
Gong, L., Goswami, S., Giacomini, K. M., Altman, R. B., & Klein, T. E. (2012) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e3283559b22 · Cited by 495
Nies, A. T., Koepsell, H., Damme, K., & Schwab, M. (2011) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-14541-4_3 · Cited by 375
Srivastava, R. A. K., Pinkosky, S. L., Filippov, S., Hanselman, J. C., Cramer, C. T., & Newton, R. S. (2012) · Journal of Lipid Research · doi:10.1194/jlr.r025882 · Cited by 296
Metadata
- Authors
- Becker, M. L., Visser, L. E., van Schaik, R. H. N., Hofman, A., Uitterlinden, A. G., & Stricker, B. H. C.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2009-03-01
- Volume
- 58
- Issue
- 3
- Pages
- 745-749
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2110289717
- Cited by
- 290
- References
- 4
- FWCI
- 20.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Becker, M. L., Visser, L. E., van Schaik, R. H. N., Hofman, A., Uitterlinden, A. G., & Stricker, B. H. C. (2009). Genetic Variation in the Multidrug and Toxin Extrusion 1 Transporter Protein Influences the Glucose-Lowering Effect of Metformin in Patients With Diabetes: A Preliminary Study. Diabetes. https://doi.org/10.2337/db08-1028
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