First Gene Found Linked to Heart Attack Risk

Scientists have identified the first gene linked to the common form of heart attack and have found that it confers about a twofold increased risk while also increasing the risk of stroke. The findings were reported in the February 9, 2004, online issue of Nature Genetics.

Researchers from deCode Genetics (Reykjavik, Iceland) identified the at-risk haplotype through the analysis of detailed genotypic data from several thousand patients and unaffected relatives in Iceland participating in the company's cardiovascular disease programs. Analysis of a linkage peak on chromosome 13 with a dense set of single nucleotide polymorphisms (SNPs) revealed a four-SNP haplotype spanning the gene encoding 5-lipoxygenase activating protein, or FLAP (ALOX5AP), which confers about a twofold increased risk of heart attack. By genotyping and comparing the same SNPs in a large group of Icelandic stroke patients with a significantly higher risk of stroke, the same haplotype was also found to correlate with a significantly higher risk of stroke. The researchers also worked with UK doctors analyzing genotypic data from 1,500 British heart attack patients and control and found a similar risk associated with variations in the gene encoding FLAP, but with a different four-SNP haplotype.

Research by the decode team combined with prior studies suggest that upregulation of the gene encoding FLAP may contribute to the inflammation and rupture of atherosclerotic plaque, a common event directly preceding both heart attack and stroke. deCode says its findings suggest that inhibiting the activity of FLAP may thus be an effective means of reducing inflammation and thereby preventing the development of heart attacks and stroke. In fact, deCode has in-licensed a compound, DG031, designed to inhibit FLAP, and clinical trials are being planned.




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