New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid: an observational study

Lukasz Milanowski, Justyna Pordzik, Piotr K. Janicki, Agnieszka Kaplon-Cieslicka, Marek Rosiak, Michal Peller, Agata Tyminska, Krzysztof Ozieranski, Krzysztof J. Filipiak, Grzegorz Opolski, Dagmara Mirowska-Guzel, Marek Postula

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Aims: Genetic polymorphisms may contribute to platelet reactivity in diabetic patients; however, the information on their influence on long-term antiplatelet therapy is lacking. Our aim was to evaluate the role of previously described genetic variants and platelet reactivity on risk of all-cause mortality and cardiovascular events. Methods: Blood samples were obtained from 303 Caucasian patients. Genome-wide genotyping was performed using Illumina Human Omni 2.5-Quad microarrays, and individual genotyping of selected SNPs was performed using a custom Sequenom iPLEX assay in conjunction with the Mass ARRAY platform. Platelet reactivity was measured with VerifyNow Aspirin Assay and PFA-100 Assay. Univariate and multivariate Cox regression analyses were performed to determine the impact of genetic variants and platelets reactivity on risk of all-cause mortality and cardiovascular events. Results: Among the 237 patients included in the follow-up, death from any cause occurred in 34 (14.3%) patients and cardiovascular events occurred in 51 (21.5%) patients within a median observation time of 71 months (5.9 years). In univariate analyses, significant association in the presence of minor alleles in TXBA2R (rs1131882) with primary (HR 2.54, 95% CI 1.15–5.60, p = 0.021) and secondary endpoint (HR 2.06, 95% CI 1.06–4.04, p = 0.034) was observed. In addition, multivariate analyses revealed the impact of this polymorphism on primary (HR 2.34, 95% CI 1.09–5.00, p = 0.029) and secondary endpoint (HR 1.89, 95% CI 1.00–3.57, p = 0.048). Conclusions: Results of the study demonstrate for the first time an association between genetic polymorphism within TXBA2R gene encoding platelet’s surface receptor and long-term survival of diabetic patients treated with ASA.

Original languageEnglish (US)
Pages (from-to)343-351
Number of pages9
JournalActa Diabetologica
Volume54
Issue number4
DOIs
StatePublished - Apr 1 2017

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Type 2 Diabetes Mellitus
Aspirin
Observational Studies
Single Nucleotide Polymorphism
Blood Platelets
Survival
Genetic Polymorphisms
Mortality
Cause of Death
Multivariate Analysis
Alleles
Regression Analysis
Observation
Genome
Genes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Milanowski, Lukasz ; Pordzik, Justyna ; Janicki, Piotr K. ; Kaplon-Cieslicka, Agnieszka ; Rosiak, Marek ; Peller, Michal ; Tyminska, Agata ; Ozieranski, Krzysztof ; Filipiak, Krzysztof J. ; Opolski, Grzegorz ; Mirowska-Guzel, Dagmara ; Postula, Marek. / New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid : an observational study. In: Acta Diabetologica. 2017 ; Vol. 54, No. 4. pp. 343-351.
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title = "New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid: an observational study",
abstract = "Aims: Genetic polymorphisms may contribute to platelet reactivity in diabetic patients; however, the information on their influence on long-term antiplatelet therapy is lacking. Our aim was to evaluate the role of previously described genetic variants and platelet reactivity on risk of all-cause mortality and cardiovascular events. Methods: Blood samples were obtained from 303 Caucasian patients. Genome-wide genotyping was performed using Illumina Human Omni 2.5-Quad microarrays, and individual genotyping of selected SNPs was performed using a custom Sequenom iPLEX assay in conjunction with the Mass ARRAY platform. Platelet reactivity was measured with VerifyNow Aspirin Assay and PFA-100 Assay. Univariate and multivariate Cox regression analyses were performed to determine the impact of genetic variants and platelets reactivity on risk of all-cause mortality and cardiovascular events. Results: Among the 237 patients included in the follow-up, death from any cause occurred in 34 (14.3{\%}) patients and cardiovascular events occurred in 51 (21.5{\%}) patients within a median observation time of 71 months (5.9 years). In univariate analyses, significant association in the presence of minor alleles in TXBA2R (rs1131882) with primary (HR 2.54, 95{\%} CI 1.15–5.60, p = 0.021) and secondary endpoint (HR 2.06, 95{\%} CI 1.06–4.04, p = 0.034) was observed. In addition, multivariate analyses revealed the impact of this polymorphism on primary (HR 2.34, 95{\%} CI 1.09–5.00, p = 0.029) and secondary endpoint (HR 1.89, 95{\%} CI 1.00–3.57, p = 0.048). Conclusions: Results of the study demonstrate for the first time an association between genetic polymorphism within TXBA2R gene encoding platelet’s surface receptor and long-term survival of diabetic patients treated with ASA.",
author = "Lukasz Milanowski and Justyna Pordzik and Janicki, {Piotr K.} and Agnieszka Kaplon-Cieslicka and Marek Rosiak and Michal Peller and Agata Tyminska and Krzysztof Ozieranski and Filipiak, {Krzysztof J.} and Grzegorz Opolski and Dagmara Mirowska-Guzel and Marek Postula",
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Milanowski, L, Pordzik, J, Janicki, PK, Kaplon-Cieslicka, A, Rosiak, M, Peller, M, Tyminska, A, Ozieranski, K, Filipiak, KJ, Opolski, G, Mirowska-Guzel, D & Postula, M 2017, 'New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid: an observational study', Acta Diabetologica, vol. 54, no. 4, pp. 343-351. https://doi.org/10.1007/s00592-016-0945-y

New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid : an observational study. / Milanowski, Lukasz; Pordzik, Justyna; Janicki, Piotr K.; Kaplon-Cieslicka, Agnieszka; Rosiak, Marek; Peller, Michal; Tyminska, Agata; Ozieranski, Krzysztof; Filipiak, Krzysztof J.; Opolski, Grzegorz; Mirowska-Guzel, Dagmara; Postula, Marek.

In: Acta Diabetologica, Vol. 54, No. 4, 01.04.2017, p. 343-351.

Research output: Contribution to journalArticle

TY - JOUR

T1 - New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid

T2 - an observational study

AU - Milanowski, Lukasz

AU - Pordzik, Justyna

AU - Janicki, Piotr K.

AU - Kaplon-Cieslicka, Agnieszka

AU - Rosiak, Marek

AU - Peller, Michal

AU - Tyminska, Agata

AU - Ozieranski, Krzysztof

AU - Filipiak, Krzysztof J.

AU - Opolski, Grzegorz

AU - Mirowska-Guzel, Dagmara

AU - Postula, Marek

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Aims: Genetic polymorphisms may contribute to platelet reactivity in diabetic patients; however, the information on their influence on long-term antiplatelet therapy is lacking. Our aim was to evaluate the role of previously described genetic variants and platelet reactivity on risk of all-cause mortality and cardiovascular events. Methods: Blood samples were obtained from 303 Caucasian patients. Genome-wide genotyping was performed using Illumina Human Omni 2.5-Quad microarrays, and individual genotyping of selected SNPs was performed using a custom Sequenom iPLEX assay in conjunction with the Mass ARRAY platform. Platelet reactivity was measured with VerifyNow Aspirin Assay and PFA-100 Assay. Univariate and multivariate Cox regression analyses were performed to determine the impact of genetic variants and platelets reactivity on risk of all-cause mortality and cardiovascular events. Results: Among the 237 patients included in the follow-up, death from any cause occurred in 34 (14.3%) patients and cardiovascular events occurred in 51 (21.5%) patients within a median observation time of 71 months (5.9 years). In univariate analyses, significant association in the presence of minor alleles in TXBA2R (rs1131882) with primary (HR 2.54, 95% CI 1.15–5.60, p = 0.021) and secondary endpoint (HR 2.06, 95% CI 1.06–4.04, p = 0.034) was observed. In addition, multivariate analyses revealed the impact of this polymorphism on primary (HR 2.34, 95% CI 1.09–5.00, p = 0.029) and secondary endpoint (HR 1.89, 95% CI 1.00–3.57, p = 0.048). Conclusions: Results of the study demonstrate for the first time an association between genetic polymorphism within TXBA2R gene encoding platelet’s surface receptor and long-term survival of diabetic patients treated with ASA.

AB - Aims: Genetic polymorphisms may contribute to platelet reactivity in diabetic patients; however, the information on their influence on long-term antiplatelet therapy is lacking. Our aim was to evaluate the role of previously described genetic variants and platelet reactivity on risk of all-cause mortality and cardiovascular events. Methods: Blood samples were obtained from 303 Caucasian patients. Genome-wide genotyping was performed using Illumina Human Omni 2.5-Quad microarrays, and individual genotyping of selected SNPs was performed using a custom Sequenom iPLEX assay in conjunction with the Mass ARRAY platform. Platelet reactivity was measured with VerifyNow Aspirin Assay and PFA-100 Assay. Univariate and multivariate Cox regression analyses were performed to determine the impact of genetic variants and platelets reactivity on risk of all-cause mortality and cardiovascular events. Results: Among the 237 patients included in the follow-up, death from any cause occurred in 34 (14.3%) patients and cardiovascular events occurred in 51 (21.5%) patients within a median observation time of 71 months (5.9 years). In univariate analyses, significant association in the presence of minor alleles in TXBA2R (rs1131882) with primary (HR 2.54, 95% CI 1.15–5.60, p = 0.021) and secondary endpoint (HR 2.06, 95% CI 1.06–4.04, p = 0.034) was observed. In addition, multivariate analyses revealed the impact of this polymorphism on primary (HR 2.34, 95% CI 1.09–5.00, p = 0.029) and secondary endpoint (HR 1.89, 95% CI 1.00–3.57, p = 0.048). Conclusions: Results of the study demonstrate for the first time an association between genetic polymorphism within TXBA2R gene encoding platelet’s surface receptor and long-term survival of diabetic patients treated with ASA.

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