London: An international team of scientists has identified 13 new gene sites associated with the risk of coronary artery disease and validated 10 sites found in previous studies.
"We now have identifed 23 specific genetic ``letters`` that appear to confer risk for myocardial infarction and other aspects of coronary artery disease," said Sekar Kathiresan at Massachusetts General Hospital.
"Knowing these sites lays the groundwork for isolating the genes responsible and developing new treatments based on those genes."
The team of 167 investigators at research centers around the world formed the Coronary ARtery DIsease Genomewide Replication and Meta-analysis (CARDIoGRAM) Consortium.
The researchers first assembled data from 14 previous GWAS (genome-wide association studies) for meta-analysis. They reviewed data from more than 22,000 individual with heart disease and almost 65,000 controls.
The most promising sites identifed in the meta-analysis were then genotyped in another group of more than 56,600 individuals, about half with cardiac disease. The investigators also analyzed potential mechanisms and metabolic pathways by which newly identified variants might affect risk.
Results showed that 10 of 12 previously reported gene variants associated with coronary artery disease and identified 13 sites not previously reported.
Of the 23 variants validated in this study, seven are associated with LDL cholesterol levels and one with hypertension, but the others have no relation to known cardiovascular risk factors.
"The lack of apparent association with the risk factors we know so well is the source of a lot of excitement concerning these results," Kathiresan explained.
"If these variants do not act through known mechanisms, how do they confer risk for heart disease? It suggests there are new mechanisms we don``t yet understand. Another good thing about these findings is that they are in human patients, not in cells or mice, which gives us a good starting point for figuring out new disease pathways."
The study appears in Nature Genetics.