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Few gene variants associated with acute coronary syndrome are tied to increased deaths among such patients

Many gene variants have been suggested to increase the risk of acute coronary syndrome (ACS)-unstable angina or two specific types of heart attack-but none has been conclusively shown to affect survival following the acute event. A new study, which examined the link between death within 3 years of ACS and the presence in patients of any of 89 genetic variants in 79 genes, found 16 genetic variants potentially associated with increased mortality. Only one gene variant, a variant of insulin receptor substrate 1 (IRS1), had results that remained close to statistical significance after correction for traditional cardiac risk factors and multiple comparisons. The researchers studied 811 patients with ACS seen at two hospitals in Kansas City, Missouri, from March 2001 through June 2003, who underwent genotyping. The researchers followed them for at least 3 years to record deaths among them.

A family history of coronary artery disease or heart attack was found in slightly more than half the patients. Ninety patients died. Two sets of genetic variants associated with the occurrence of ACS in the study population were not linked with death following ACS.

The researchers conclude that retesting 73 of the genetic variants in a larger patient population was not likely to reveal a strong association with post-ACS death risk. Although three of the remaining gene variants (in the ACE, F7, and ICAM1 genes) were previously shown to be protective against the occurrence of ACS, they appeared to increase slightly the risk of death in patients who do develop the condition.

Because IRS1 is a protein that binds to the insulin receptor, the researchers suggest that their findings indicate a need for further study of the mortality-increasing variant of the gene in a larger population of ACS patients, particularly those with diabetes (who would have abnormal blood insulin levels).

The study was funded in part by the Agency for Healthcare Research and Quality (HS11282). More details are in "Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome," by Thomas M. Morgan, M.D., Lan Xiao, Ph.D., Patrick Lyons, and others, in the July 12, 2008. BioMedCentral Medical Genetics 9(66).

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