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Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus

The Pharmacogenomics Journal volume 9, pages 242–247 (2009)Cite this article

Abstract

The organic cation transporter 1, encoded by the SLC22A1 gene, is responsible for the uptake of the anti-hyperglycaemic drug, metformin, in the hepatocyte. We assessed whether a genetic variation in the SLC22A1 gene is associated with the glucose-lowering effect of metformin. Incident metformin users in the Rotterdam Study, whose HbA1c measurements were available, were identified. Associations between 11 tagging single nucleotide polymorphisms in the SLC22A1 gene and change in the HbA1c level were analyzed. A total of 102 incident metformin users were included in this study sample. Except for the rs622342 A>C polymorphism, no significant differences in metformin response were observed. For each minor C allele at rs622342, the reduction in HbA1c levels was 0.28% less (95% CI 0.09–0.47, P=0.005). After Bonferroni correction, the P-value was 0.050. To conclude, genetic variation at rs622342 in the SLC22A1 gene was associated with the glucose-lowering effect of metformin in patients with diabetes mellitus.

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Acknowledgements

We thank Drs JJ Lous for making the STAR–MDC data available for our study and F Rivadeneira, PP Arp and M Jhamai for help with providing the genotyping data.

This study was supported by The Netherlands Organisation for Scientific Research (NWO) (175.01.2005.011) and by The Netherlands Genomics Initiative (NGI) (050-060-810).

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Authors and Affiliations

  1. Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands,

    M L Becker, L E Visser, A Hofman, A G Uitterlinden & B H C Stricker

  2. Department of Hospital Pharmacy, Erasmus MC, Rotterdam, The Netherlands,

    M L Becker & L E Visser

  3. Department of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands,

    R H N van Schaik

  4. STAR Medical Diagnostic Center, Rotterdam, The Netherlands

    R H N van Schaik

  5. Member of The Netherlands Consortium on Healthy Aging, Leiden/Rotterdam, The Netherlands

    A Hofman, A G Uitterlinden & B H C Stricker

  6. Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands,

    A G Uitterlinden & B H C Stricker

  7. Drug Safety Unit, Inspectorate for Health Care, The Hague, The Netherlands

    B H C Stricker

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  1. M L Becker
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  2. L E Visser
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  3. R H N van Schaik
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  4. A Hofman
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  5. A G Uitterlinden
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  6. B H C Stricker
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Correspondence to B H C Stricker.

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Becker, M., Visser, L., van Schaik, R. et al. Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus. Pharmacogenomics J 9, 242–247 (2009). https://doi.org/10.1038/tpj.2009.15

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