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Association of platelet ITGA2B and ITGB3 polymorphisms with ex vivo antiplatelet effect of ticagrelor in healthy Chinese male subjects

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Abstract

Ticagrelor (TIC) is the first reversible P2Y12 receptor antagonist that exhibits rapid antiplatelet effect by indirect inhibition of the GPIIb/IIIa complex. Polymorphisms in genes coding GPIIb/IIIa, namely ITGA2B and ITGB3, are associated with aspirin resistance and risk for thrombotic diseases. We assessed whether ITGA2B and ITGB3 polymorphisms can influence the ex vivo antiplatelet activity of ticagrelor in Chinese population. A total of 196 healthy Chinese male individuals were recruited. ADP-induced platelet aggregation was determined using optical aggregometry at baseline and after incubation of the platelet-rich plasma with 15 and 50 μM ticagrelor, respectively. Single nucleotide polymorphisms in ITGA2B (rs5911 G>T) and ITGB3 (rs4642 A>G and rs4634 G>A) were genotyped by sequencing. TIC at both concentrations of 15 and 50 μM decreased ADP-induced platelet aggregation significantly (P < 0.05, respectively). As compared to ITGA2B rs5911 GG homozygotes, individuals with the rs5911 TG genotype showed significantly increased inhibition of platelet aggregation (IPA) by both 15 and 50 μM ticagrelor incubation (P < 0.05, respectively). Neither rs4642 nor rs4634 polymorphism affected ticagrelor-induced IPA. We suggest that the ITGA2B rs5911 GG genotype is associated with decreased ex vivo antiplatelet activity of ticagrelor in healthy Chinese male subjects.

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Acknowledgments

This project was supported by Chinese National Science Foundation (No. 81170091), Special topic of the major subject of national science and technology (2012ZX09509-107), Funds for the Central Universities (2011JQ016), Hunan Provincial Natural Science Foundation of China (13JJ1010), and Funds for Hunan education department program (No. 12K006).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Clinical Pharmacology, Central South University, Changsha, 410078, Hunan, China

    Mu-Peng Li, Yan Xiong, Ji-Peng Zhou, Jie Tang, Hong-Hao Zhou, Wei Zhang & Xiao-Ping Chen

  2. School of Pharmaceutical Science, Central South University, Changsha, 410078, Hunan, China

    An Xu

  3. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, China

    Zan-Ling Zhang

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  1. Mu-Peng Li
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Li, MP., Xiong, Y., Xu, A. et al. Association of platelet ITGA2B and ITGB3 polymorphisms with ex vivo antiplatelet effect of ticagrelor in healthy Chinese male subjects. Int J Hematol 99, 263–271 (2014). https://doi.org/10.1007/s12185-014-1502-5

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