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New single nucleotide polymorphisms associated with differences in platelets reactivity in patients with type 2 diabetes treated with acetylsalicylic acid: genome-wide association approach and pooled DNA strategy

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Abstract

The objective of this study was to use genome-wide association approach and pooled DNA strategy to search for new genomic loci associated with inter-individual differences in platelet reactivity in the diabetic patients during acetylsalicylic acid (ASA) treatment. Study cohort consisted of 297 diabetic patients who had been taking ASA (75 mg daily) for at least 3 months. We tested association of single nucleotide polymorphisms (SNPs) genotyped using high density microarray platform with several platelet reactivity assays, followed by individual genotyping of most significant SNPs identified in the microarray genomic scan. The highest statistical significance (p value of 0.0001–0.008 in individual genotyping) was observed for SNP located within the regulatory G-protein signaling (RGS) 7 gene (rs2502448) using recessive genetic model. The diabetic patients on ASA treatment and homozygotes for its minor allele were characterized by increased odds ratio of at 3.45 (confidence interval: 1.82–6.53) for high on ASA platelet reactivity (i.e. impaired ASA response) when compared with homozygotes for wild-type allele. The genome-wide approach might provide an opportunity to identify novel candidate genes and pathways related to platelet activation in diabetic patients.

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Acknowledgments

Dr Postula was supported by a Fulbright Fellowship from USA State Department. The AVOCADO study was supported financially as part of the research grant from the Polish Pharmaceutical Company ADAMED for a Young Scientist 2007 Award [grant number: 1WR DAR1/2007] and Polish Cardiac Society Club 30 grant 2010. The authors thank Thutrang Nguyen, B.A. from the SNP Genotyping Core Facility at Children’s Hospital Boston, Massachusetts, for performing the custom Sequenom iPLEX assay.

Disclosure of conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, 26/28 Krakowskie Przedmiescie, 02-927, Warsaw, Poland

    Marek Postula & Andrzej Czlonkowski

  2. Perioperative Genomics Laboratory, Department of Anesthesiology, Penn State College of Medicine, Hershey, Pennsylvania, USA

    Piotr K. Janicki

  3. Department of Cardiology, Medical University of Warsaw, Independent Public Central Clinical Hospital in Warsaw, 1a Banacha St., 02-097, Warsaw, Poland

    Marek Postula, Marek Rosiak, Agnieszka Kaplon-Cieslicka, Ewa Trzepla, Krzysztof J. Filipiak & Grzegorz Opolski

  4. Department of Noninvasive Cardiology and Hypertension, Central Clinical Hospital, The Ministry of the Interior, 137 Woloska St., 02-507, Warsaw, Poland

    Dariusz A. Kosior

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  1. Marek Postula
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  2. Piotr K. Janicki
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Corresponding author

Correspondence to Marek Postula.

Additional information

Marek Postula and Piotr K. Janicki contributed equally to this study.

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Postula, M., Janicki, P.K., Rosiak, M. et al. New single nucleotide polymorphisms associated with differences in platelets reactivity in patients with type 2 diabetes treated with acetylsalicylic acid: genome-wide association approach and pooled DNA strategy. J Thromb Thrombolysis 36, 65–73 (2013). https://doi.org/10.1007/s11239-012-0823-6

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