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Genetic markers predicting sulphonylurea treatment outcomes in type 2 diabetes patients: current evidence and challenges for clinical implementation

The Pharmacogenomics Journal volume 16, pages 209219 (2016) | Download Citation

Abstract

The clinical response to sulphonylurea, an oral antidiabetic agent often used in combination with metformin to control blood glucose in type 2 diabetes (T2DM) patients, has been widely associated with a number of gene polymorphisms, particularly those involved in insulin release. We have reviewed the genetic markers of CYP2C9, ABCC8, KCNJ11, TCF7L2 (transcription factor 7-like 2), IRS-1 (insulin receptor substrate-1), CDKAL1, CDKN2A/2B, KCNQ1 and NOS1AP (nitric oxide synthase 1 adaptor protein) genes that predict treatment outcomes of sulphonylurea therapy. A convincing pattern for poor sulphonylurea response was observed in Caucasian T2DM patients with rs7903146 and rs1801278 polymorphisms of the TCF7L2 and IRS-1 genes, respectively. However, limitations in evaluating the available studies including dissimilarities in study design, definitions of clinical end points, sample sizes and types and doses of sulphonylureas used as well as ethnic variability make the clinical applications challenging. Future studies need to address these limitations to develop personalized sulphonylurea medicine for T2DM management.

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Acknowledgements

This study received funding from the University of Malaya, Malaysia (University of Malaya Research Grant RP024-14HTM and Postgraduate Research Grant PG056-2014A) and also Doctor of Philosophy scholarship award from the Ministry of Health, Malaysia.

Author information

Affiliations

  1. Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

    • N K Loganadan
    •  & H Z Huri
  2. Clinical Investigation Centre, University of Malaya Medical Centre, Kuala Lumpur, Malaysia

    • H Z Huri
  3. Endocrinology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

    • S R Vethakkan
  4. Department of Medicine, Putrajaya Hospital, Putrajaya, Malaysia

    • Z Hussein

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to H Z Huri.

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DOI

https://doi.org/10.1038/tpj.2015.95

Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj)