Genotyp-Phänotyp-Assoziation von drei kardiovaskulären Kandidatengenen unter Berücksichtigung der kardiovaskulären Risikofaktoren in Hinblick auf die Prävalenz des Myokardinfarkts bei jungen Patienten

Multi factorial diseases like the coronary heart disease including the myocardial infarction are caused by a complex interaction of genetic and exogenic (meaning environmental, behavior based and sociocultural) factors. To determine the effect of the so called genetic polymorphism of cardiovascular phenotypes it is reasonable to analyze large homogeneous and accurately characterized populations. Only by using this method even small effects can be detected that contribute to the cause of myocardial infarcts. In such polymorphism-association-studies it is important to record the exogenic factors systematically because they can potentially impact the association between the genotype and phenotype. In this study 3436 patients of the RWTH Aachen university clinic were recruited. They were admitted with the clinical indication of their first intra cardiac catheter without a prior diagnosed coronary heart disease or any other non ischaemic cardiomyopathy and were of the same ethnic background. These patients were divided by age (patients younger than 65 years of age = high genetic influence / patients above 65 years of age = little genetic influence) and for each patient a thorough, cardiological determination of phenotypes was performed using coronary angiography, cineventriculographie and clinical parameters. Furthermore the classical cardiovascular risk factors (CRF = arterial hypertension, diabetes mellitus, hypercholesterolemia and smoking) were recorded and three candidate genes ( Interleukin-6 G-174C, Vitamin C-receptor Bsml and chemokine-receptor-2-V641-genetic polymorphism) belonging to the inflammatory system and therefore important for the pathophysiology of the coronary heart disease were analyzed. Finally a combined analysis of genetic and cardiovascular risk factors with regards to the prevalence of the myocardial infarction by stratification of the patient (potentially high genetic influence versus potential low genetic influence) was made. The myocardial infarction before the age of 65 was defined as a premature myocardial infarction. A significant correlation of individual allele of the genetic polymorphism (VDR BB, Il6 GC/CC, CCR2 VI/II) with high occurrences of myocardial infarctions became evident in the patient group younger than 65 (n= 1946). In our study these polymorphism were defined as genetic risk factors. A combined analysis of the four classic cardiovascular risk factors and the three genetic risk factors showed an additive effect regarding the occurrence of a myocardial infarction. The more risk factors (CRF + GRF; from 0-7) were present, the higher was the prevalence of the myocardial infarction. The patient's age was not associated with the infarcton in this group. In the patient group older than 65 years of age the combined analysis of the CRF risk factors showed only a weak correlation with the prevalence of a myocardial infarction. The examination of the GRF showed no correlation at all. In these patient groups the age was the main parameter for the development of a myocardial infarction. The presented examination allows the conclusion that certain genetic risk factors have an additive -if only a weak – effect on the predisposition of the development of a premature myocardial infarction. The tested genetic risk factors showed no effect on the patient group older than 65 years of age. Due to the very weak detectable effect of the tested genetic polymorphism it remains unclear, which relevance the test of GRF will have in the future and which direction it will take. The currant knowledge does not allow any improvement of the therapy by testing the GRF in the daily clinical routine.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2009

Author dc:creator

• Krantz, Constanze

Contributors dc:contributor

• Ortlepp, Jan Rudolf

• info:eu-repo/classification/ddc/610
• Genotyp
• Phänotyp
• Assoziation
• Herzinfarkt
• Prävalenz
• Medizin
• kardiovaskuläre Risikofaktoren
• genetische Polymorphismen
• genotype
• phenotype
• genetic polymorphism
• myocardial Infarction
• cardiovascular risk factors
• prevalence

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113705%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51413