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

Marek Postula, Piotr K. Janicki, Marek Rosiak, Agnieszka Kaplon-Cieslicka, Ewa Trzepla, Krzysztof J. Filipiak, Dariusz A. Kosior, Andrzej Czlonkowski, Grzegorz Opolski

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)65-73
Number of pages9
JournalJournal of Thrombosis and Thrombolysis
Volume36
Issue number1
DOIs
StatePublished - Jul 1 2013

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Type 2 Diabetes Mellitus
Aspirin
Single Nucleotide Polymorphism
Blood Platelets
Genome
DNA
Homozygote
Alleles
Genetic Models
Platelet Activation
GTP-Binding Proteins
Individuality
Genes
Cohort Studies
Odds Ratio
Confidence Intervals
Therapeutics

All Science Journal Classification (ASJC) codes

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Postula, Marek ; Janicki, Piotr K. ; Rosiak, Marek ; Kaplon-Cieslicka, Agnieszka ; Trzepla, Ewa ; Filipiak, Krzysztof J. ; Kosior, Dariusz A. ; Czlonkowski, Andrzej ; Opolski, Grzegorz. / 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. In: Journal of Thrombosis and Thrombolysis. 2013 ; Vol. 36, No. 1. pp. 65-73.
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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. / Postula, Marek; Janicki, Piotr K.; Rosiak, Marek; Kaplon-Cieslicka, Agnieszka; Trzepla, Ewa; Filipiak, Krzysztof J.; Kosior, Dariusz A.; Czlonkowski, Andrzej; Opolski, Grzegorz.

In: Journal of Thrombosis and Thrombolysis, Vol. 36, No. 1, 01.07.2013, p. 65-73.

Research output: Contribution to journalArticle

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AU - Postula, Marek

AU - Janicki, Piotr K.

AU - Rosiak, Marek

AU - Kaplon-Cieslicka, Agnieszka

AU - Trzepla, Ewa

AU - Filipiak, Krzysztof J.

AU - Kosior, Dariusz A.

AU - Czlonkowski, Andrzej

AU - Opolski, Grzegorz

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N2 - 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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