DARWIN Digitale Dissertationen German Version Strich

FU Berlin
Digitale Dissertation

Christian Thomas Vetter :
Long-term results after PTCA with or without stent implantation according to the genotype of the Gp IIb/IIIa receptor.
Langzeitresultate nach PTCA mit/ohne Stentimplantation in Abhängigkeit vom Genotyp des Gp IIb/IIIa Rezeptors.

 FU Logo

|Abstract| |Table of Contents| |More Information|

Abstract

Background: Restenosis is a major problem after percutaneous transluminal coronary angioplasty (PTCA). The rate of restenosis is usually between 20%-30%. Arteriosclerosis plays a key role in its pathogenesis. Thrombocytes, especially the glycoprotein (Gp) IIb/IIIa receptor, the most frequently expressed receptor on thrombocytes, may play an important role in the development of restenosis following PTCA with or without stent implantation. Blocking this receptor inhibits efficiently thrombocyte aggregation. Several polymorphisms of the Gp IIb/IIIa have been described. Among others, the PlA1/A2 polymorphism is characterised by a base exchange, which leads to an amino acid exchange in the protein (leucin33 vs. prolin33). The clinical value of the PlA1/A2 polymorphism is still debated, and to gain further insight we conducted a retrospective molecular genetic analysis to assess its role in promoting restenosis. Hypothesis: PlA1/A2 polymorphism, especially the PlA2 allele, promotes restenosis after PTCA with or without stent implantation. Methods: 996 consecutive patients (pts) who underwent coronary angiography were included in this study. During a follow-up of 18 months, 202 pts had a new coronary angiography: 115 pts had restenosis (group 1) and 87 pts did not (group 2). A third group was arbitrarily created with 98 pts who were free of coronary artery disease (group 3). Pts were further classified according to the number of vessel diseased. Blood samples were drawn and molecular genetic investigations performed with the help of polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). Prevalence of restenosis was correlated with the PlA1/A2 polymorphism. Results: Compared to the group without restenosis (group 2) and the group without coronary artery disease (group 3), the prevalence of the PlA1/A2 polymorphism, especially the PlA2 allele, was not increased in the group with restenosis (group 1) (p=0.48). Pts with multi-vessel disease had a statistically significant higher risk of restenosis compared with pts with a one-vessel disease (p=0.03). Conclusions: PlA1/A2 polymorphism does not influence the long-term development of coronary restenosis after PTCA with or without stent implantation. Multi-vessel disease predicts a higher rate of restenosis than single-vessel disease, independently of PlA1/A2 polymorphism.

Table of Contents

Download the whole PhDthesis as a zip-tar file or as zip-File

For download in PDF format click the chapter title

0. Titelblatt
1. Einleitung 6
1.1. Koronare Herzkrankheit und Restenose 6
1.2. Weiterführende Diagnostik in der Behandlung der KHK 10
1.2.1. Quantitative Koronaranalyse (QCA) 10
1.2.2. Intravaskulärer Ultraschall (IVUS) 12
1.3. Atherosklerose 14
1.4. Risikofaktoren für die Restenoseentstehung 15
1.5. Pathophysiologie der Restenose 18
1.6. Integrine 22
1.6.1. Gp IIb/IIIa Rezeptor 25
1.6.2. Bindungsstellen des Gp IIb/IIIa Rezeptors 28
1.6.3. PlA1/A2 Polymorphismus 30
1.6.4. Gp IIb/IIIa Rezeptorantagonisten 33
1.6.5. Glanzmann-Naegeli-Syndrom 36
1.7. Ziel der Arbeit 37
2. Hauptteil 42
2.1. Material und Methoden 42
2.2. Molekulargenetische Untersuchungen 44
2.2.1. Polymerasekettenreaktion (PCR) 45
2.2.2. Restriktionslängenpolymorphismus (RFLP) 47
2.3. Ergebnisse 49
2.3.1. Charakterisierung des Patientenkollektivs 49
2.3.2. Analyse der QCA im Subkollektiv 53
2.3.3. Einzelfalldarstellung 53
2.4. Statistik 59
3. Diskussion 66
3.1.1 Kosten- und Nutzenanalyse 73
4. Schlussfolgerung 77
5. Zusammenfassung 80
6. Abkürzungen und Erklärungen 83
7. Literaturverzeichnis 85
8. Anhang 114
8.1. Grafische Ergebnisdarstellung 114
9. Danksagung 116

More Information:

Online available: http://www.diss.fu-berlin.de/2002/122/indexe.html
Language of PhDThesis: german
Keywords: PTCA ¿ stent implantation - restenosis - Gp IIb/IIIa receptor - PlA1/A2 polymorphism.
DNB-Sachgruppe: 33 Medizin
Date of disputation: 17-May-2002
PhDThesis from: Fachbereich Humanmedizin, Freie Universität Berlin
First Referee: Prof. Dr. med. Wolfgang Poller
Second Referee: PD Dr. Bernd Ramdohr
Contact (Author): cvetter@freenet.de
Contact (Advisor): 100270.2245@compuserve.com
Date created:15-Jul-2002
Date available:18-Jul-2002

 

|| DARWIN|| Digitale Dissertationen || Dissertation|| German Version|| FU Berlin|| Seitenanfang ||

Mail-Icon Fragen und Kommentare an:
darwin@inf.fu-berlin.de

© Freie Universität Berlin 1999