Genetics of myocardial infarction: a progress report.
A small region on chromosome 9p21.3, discovered in parallel by three groups in the year 2007, is typical of the new understanding of the genetic basis of myocardial infarction (MI). The finding emerged from the application of novel high-throughput genome-wide approaches, the risk-associated allele is frequent, acts independently of traditional risk factors, and confers a modest yet highly reproducible hazard. Since then, another 10 chromosomal regions have been identified to affect the risk of MI or coronary artery disease (CAD). Although the number of risk alleles is growing rapidly, several conclusions can already be drawn from the findings to date. First, it appears that multiple hitherto unknown molecular mechanisms--initiated by these chromosomal variants--ultimately precipitate CAD. Secondly, essentially all Caucasians carry a variable number of risk alleles such that disease manifestation is affected to some extent by these inherited factors in basically all individuals. This means that a better understanding of underlying functional genomic mechanisms may offer novel opportunities to neutralize a broadly based genetic susceptibility for CAD in a large proportion of the population. In parallel, the newly discovered genes open novel opportunities for disease prediction. In summary, modern MI genetics carries the promise to identify individuals at high risk and to improve prevention and therapy of this important disease.
Schunkert
Heribert
H
Universität zu Lübeck, Medizinische Klinik II, Ratzeburger Allee 160, 23538 Lübeck, Germany. heribert.schunkert@uk-sh.de
Erdmann
Jeanette
J
Samani
Nilesh J
NJ
D008078:Cholesterol, LDL / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics*; D005787:Gene Frequency; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D009203:Myocardial Infarction / Q000235:genetics*; D010375:Pedigree; D018570:Risk Assessment
D008078:Cholesterol, LDL