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Pharmacogenetics of oral antidiabetes drugs: evidence for diverse signals at the IRS1 locus

The Pharmacogenomics Journal volume 18, pages 431–435 (2018)Cite this article

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Abstract

To investigate the role of IRS1 locus on failure to oral antidiabetes drugs (OADs) we genotyped single-nucleotide polymorphisms (SNPs), rs2943641, rs7578326 (tagging all SNPs genome-wide associated with type 2 diabetes (T2D) and related traits at this locus) and rs1801278 (that is, the loss-of-function IRS1 G972R amino acid substitution) in 2662 patients with T2D. Although no association with OAD failure was observed for rs2943641 and rs7578326 SNPs (odds ratio (OR): 1.04, 95% confidence interval (CI): 0.93–1.16 and OR: 0.97, 95% CI: 0.87–1.09 respectively), a significant association was observed for rs1801278 (OR: 1.34, 95% CI: 1.08–1.66). When meta-analyzed with previous published data, an allelic OR of 1.41 (1.15–1.72; P=0.001) was obtained, so that homozygous R972R individuals have >80% higher risk of failing to OADs as compared with their G972G counterparts. In all, though further studies are needed for confirming this finding, our present data point to IRS1 rs1801278 as a potential biomarker for pursuing the goal of stratified medicine in the field of antihyperglycemic treatment in T2D.

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Acknowledgements

This study was supported by the Italian Ministry of Health (Ricerca Corrente 2015 and 2016 to S Prudente, R Di Paola and V Trischitta), by the ‘5 × 1000’ voluntary contribution to IRCCS Casa Sollievo della Sofferenza, by the Italian Ministry of University and Research (PRIN 2012 and 2015 to V Trischitta), by Fondazione Roma (‘Biomedical Research: non-communicable diseases 2013 Grant’ to V Trischitta) and by EC (European project FP-7 MEDIGENE 279171 to V Trischitta).

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Authors and Affiliations

  1. Research Unit of Metabolic and Cardiovascular Diseases, IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy

    S Prudente, S Pezzilli, L Mercuri, F Alberico & V Trischitta

  2. Research Unit of Diabetes and Endocrine Diseases, IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy

    R Di Paola, M G Scarale & V Trischitta

  3. Department of Experimental Medicine, ‘Sapienza’ University, Rome, Italy

    S Pezzilli, T Filardi, S Morano & V Trischitta

  4. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    M Garofolo & G Penno

  5. Department of Medical and Surgical Sciences, Unit of Endocrinology, University of Foggia, Foggia, Italy

    O Lamacchia & M Cignarelli

  6. Department of Medical and Surgeon Science, University Magna Graecia, Catanzaro, Italy

    G C Mannino & G Sesti

  7. Unit of Biostatistics, IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy

    M G Scarale & M Copetti

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  1. S Prudente
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  8. L Mercuri
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Correspondence to S Prudente or V Trischitta.

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Prudente, S., Di Paola, R., Pezzilli, S. et al. Pharmacogenetics of oral antidiabetes drugs: evidence for diverse signals at the IRS1 locus. Pharmacogenomics J 18, 431–435 (2018). https://doi.org/10.1038/tpj.2017.32

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