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Association of PAX4 genetic variants with oral antidiabetic drugs efficacy in Chinese type 2 diabetes patients

The Pharmacogenomics Journal volume 14, pages 488–492 (2014)Cite this article

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Abstract

The aim of this study was to investigate the association of PAX4 variants with therapeutic effect of oral antidiabetic drugs in Chinese type 2 diabtes mellitus (T2DM) patients. A total of 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the therapeutic effects were compared. In the rosiglitazone cohort, rs6467136 GA+AA carriers showed greater decrease in 2-h glucose levels (P=0.0063) and higher cumulative attainment rates of target 2-h glucose levels (Plog rank=0.0093) than GG homozygotes. In the subgroup with defective β-cell function, rs6467136 GA+AA carriers exhibited greater decrements of 2-h glucose level and improvement of homeostasis model assessment of insulin resistance (P=0.0143). Moreover, GA+AA carriers were more likely to attain the target fasting and 2-h glucose level (Plog rank=0.0091 and 0.007, respectively). However, these single-nucleotide polymorphisms showed no effect on repaglinide efficacy. In conclusion, PAX4 variant rs6467136 was associated with the therapeutic effect of rosiglitazone in Chinese T2DM patients.

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Acknowledgements

We thank all the patients who participated in this study and are appreciative of the doctors and nurses at the Shanghai Clinical Center for Diabetes. This project was funded by 973 Program (2011CB504001), grants from NSFC (81322010, 81170735 and 81200582), the Drug Innovation Program of the National Science and Technology Project (2011ZX09307-001-02), 863 Program (2012AA02A509), Excellent Young Medical Expert of Shanghai (XYQ2011041), Shanghai Talent Development Grant (2012041), Shanghai Raising Star Program (12QH1401700) and National Young Top Talent Supporting Program.

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  1. M Chen and C Hu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai, China

    M Chen, C Hu, R Zhang, F Jiang, J Wang, D Peng, S Tang, X Sun, J Yan, Y Luo, Y Bao & W Jia

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  1. M Chen
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Correspondence to W Jia.

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Chen, M., Hu, C., Zhang, R. et al. Association of PAX4 genetic variants with oral antidiabetic drugs efficacy in Chinese type 2 diabetes patients. Pharmacogenomics J 14, 488–492 (2014). https://doi.org/10.1038/tpj.2014.18

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