Die bei manchen Herzinfarkt-Patienten beobachtete positive Familienanamnese kann vielfältige genetische Ursachen haben, die mit drei Genen in Verbindung stehen, wie eine Publikation in Nature Genetics zeigt – mit neuen Einsichten in die Pathogenese, aber wenig Aussichten auf einen auf breiter Ebene anwendbaren Gentest.
Neben den „traditionellen“ Risikofaktoren wie Alter, arterielle Hypertonie, Fettstoffwechselstörungen, Diabetes mellitus, Rauchen und Übergewicht gibt es auch eine genetische Prädisposition auf den Herzinfarkt. Sie ist häufig bei Patienten vorhanden, die in relativ jungem Alter (Männer unter 50, Frauen diagnosed under 60 years) and that often several family members are affected.
The responsible genes, genetic researchers are trying in so-called genome-wide association studies (GWAS) to track down. Here, the genes of people affected, people here compared with early heart attack, and healthy.
The search focused on a growing number of known single nucleotide polymorphisms (single nucleotide polymorphism, SNP), can assign their variants sometimes certain diseases.
A first variant (PCSK9) was discovered in 2003. The gene plays a role in cholesterol metabolism. Mutations with familial hypercholesterolemia go hand in hand. A number of other risk genes was described two years ago by an international research team led by Heribert Schunkert of the University of Lübeck (NEJM 2007; 357: 443-53).
The recent study of the Myocardial Infarction Genetics Consortium heart attack increases the number of genes to nine, including three previously unknown genes on chromosomes 2, 6 and 21 (Nature Genetics 2009; doi: 10.1038/ng.327). For the current study, the group had to Sekar Kathiresan from the Massachusetts General Hospital in Boston, the genes of 26,000 patients from ten countries can be analyzed.
you had this area not only for SNP but also for so-called CNVs. These are changes in the number of Copies (copy number variants, CNV), in which individual genes on the chromosome are present.
Earlier studies had given differences in the CNV with other diseases. The trigger a heart attack come CNV, at least in the current study, however, not questioned.
contrast, combinations of adjacent SNPs seem to play a role. Such a "cluster" David-Alexandre Trégouët identified by the French research institute INSERM in Paris and employees on the chromosome 6. There, the LPA gene is located.
It regulates the concentration of lipoprotein (a) in the blood. This is one of the transport molecule for cholesterol and as such is an independent risk factor for heart attack (Nature Genetics 2009; doi: 10.1038/ng.314).
Two other risk genes discovered the group to Jeanette Erdmann of the University of Lübeck (Nature Genetics 2009; doi: 10.1038/ng.307n press). This is a variation on the one in the MRAS gene on chromosome 3, which may play a role in vascular biology. The HNF1A gene on chromosome 12 is on the other hand have a close relationship to cholesterol metabolism.
The discovered genes mainly provide new insights into the pathogenesis of heart attack or confirming the known risk constellations. This could possibly be the starting point be applied to develop new drugs.
as the basis for a genetic test to determine individual disease risk, they are likely to qualify only in exceptional cases occur, as Erdman points out in a video with the earlier publication.
the example mentioned in a younger patient with frequent heart attacks young people family tree. For giving a general population screening is currently no reason, the expert said at the time, It is likely also to change anything now. ©
heat / aerzteblatt.de
"Abstract of the study of Myocardial Infarction Genetics Consortium http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.327.html
"Abstract of the study Trégouët et al. http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.314.html
"Abstract of the study Erdmann et al. http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.307.html
»Press Releases of the Massachusetts General Hospital http://www.eurekalert.org/pub_releases/2009- 02/mgh-isi020509.php
»Press release by the University Lübeck http://idw-online.de/pages/de/news299766
» Press Cardiogenics video of the Project (to an earlier publication) http:// www.cardiogenics.eu / web / press.html
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