Genetik des Herzinfarktes und der Arteriosklerose – Neue Erkenntnisse durch genomweite Assoziationsstudien

Abstract

Coronary heart diseases and myocardial infarction are considered to be „complex diseases“ which may be triggered by genetic as well as by environmental factors. Decoding the genetic factors was most difficult in the past, since the available techniques merely enabled analysis of candidate genes, whereas these potentially important genes - as far as the disease was concerned - did not reveal any stable link-up (repeatable in different populations) (association) with the disease. However, it recently became possible - thanks to „chip technology“ developed also for genetics - to analyse relatively quickly and at a cost below 300 Euros, up to one million DNA variants of the entire genome of a person (total DNA of one person in one cell). This „genome-wide“ approach enabled identification of various genetic loci associated with coronary heart disease. These results were obtained by means of multinational meta-analytical myocardial infarction consorts. Closest association was found in a chromosomal region 9p21.3 in which only few genes were known. Even more surprising was the fact that most DNA regions associated with an increased myocardial infarction risk were not positioned in genes for traditional risk factors such as, for instance, LDL cholesterol. All risk variants identified to date represent a relatively low risk for myocardial infarction with a risk increase of 10-25 % per DNA risk variant (allelic gene). These results allow us to conclude that our present understanding of the pathophysiology of coronary heart diseases is still largely incomplete.