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Molecular Biology Reports

, Volume 46, Issue 6, pp 5695–5702 | Cite as

Integrin ß1 polymorphisms and bleeding risk after coronary artery stenting

  • M. Thienel
  • E. Lüsebrink
  • A. Kastrati
  • L. Dannenberg
  • A. Polzin
  • C. Schulz
  • S. Massberg
  • T. PetzoldEmail author
Original Article
  • 47 Downloads

Abstract

Bleeding complications following percutaneous coronary intervention associate with increased mortality. However, the underlying molecular mechanisms are insufficiently understood. Platelet recruitment and activation at sites of vascular injury depends on the function of integrin adhesion receptors. Besides GPIIbIIIa as the most abundant integrin receptor, platelets relevantly express ß1 integrins. Experimental evidence from in vivo studies suggests a significant role of ß1 integrins in primary haemostasis. However, little is known about the clinical impact of genetic alterations of the β1 subunit, which might contribute to bleeding complications in patients. In this study, we performed DNA sequencing of patients suffering from bleeding complications after coronary artery stenting according to TIMI or BARC classification. We isolated DNA samples from 741 patients out of a cohort from 14,160 patients recruited in seven randomized clinical trials between June 2000 and May 2011. Subsequently, Sanger sequencing was performed covering the β1 integrin cytoplasmic activation domain (exon16) and its non-coding upstream region. Out of 764 patients suffering from bleeding complications, 741 DNA samples were successfully sequenced. Genotype variation was detected for SNP rs2153875 located within the non-coding upstream region with following allele frequency in study population: CC (7.3%), CA (35%) and AA (57.8%), which is similar to a general population cohort. Further, genotype variation in SNP rs2153875 do not associate with the frequency of TIMI or BARC classified access or non-access site bleedings. Genotype variations of the β1 integrin activation domain do not associate with bleeding risk after PCI.

Keywords

Integrins α2ß1 Polymorphism SNP rs2153875 Bleeding risk PCI 

Abbreviations

CAD

Coronary artery disease

DAPT

Dual anti-platelet therapy

DM

Diabetes mellitus

Hb

Haemoglobin

ISAR

Intracoronary stenting and antithrombotic research regime

PCR

Polymerase chain reaction

PCT

Percutaneous coronary intervention

RCT

Randomized clinical trials

SNP

Single nucleotide polymorphism

UFH

Unfractionated heparin

Notes

Acknowledgements

The authors would like to thank the NHLBI GO Exome Sequencing Project and its ongoing studies, which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing Project (HL-103010).

Funding

This work was supported by LMU Munich’s Institutional Strategy LMU excellent within the framework of the German Excellence Initiative (TP), by the DZHK (German Center for Cardiovascular Research) to SM [Clinical Platelet Therapy Research, 81Z1600214], the LMU Munich’s Medical Faculty Förderprogramm für Forschung und Lehre (FöFoLe) (EL) and by the Forschungskommission of the Medical Faculty of the Heinrich Heine University (No. 16-2014 to A.P.; No. 46-2016 to L.D).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • M. Thienel
    • 1
    • 3
  • E. Lüsebrink
    • 1
    • 3
  • A. Kastrati
    • 2
    • 3
  • L. Dannenberg
    • 4
    • 5
  • A. Polzin
    • 4
    • 5
  • C. Schulz
    • 1
    • 3
  • S. Massberg
    • 1
    • 3
  • T. Petzold
    • 1
    • 3
    Email author
  1. 1.Medizinische Klinik und Poliklinik I, Klinikum der Universität MünchenMunichGermany
  2. 2.Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum MünchenMunichGermany
  3. 3.DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceMunichGermany
  4. 4.Klinik für Kardiologie, Pneumologie und Angiologie, Universitätsklinikum DüsseldorfDüsseldorfGermany
  5. 5.CARID (Cardiovascular Research Institute Düsseldorf)DüsseldorfGermany

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