ALOX5AP gene linked to increased risk of heart attack and stroke 10/2/04. By the Public Health Genetics Unit Icelandic researchers have identified two variants of the ALOX5AP gene that may increase the risk of heart attack and stroke.

Cardiovascular diseases such as coronary heart disease, heart attack (myocardial infarction) and stroke are the leading causes of mortality and morbidity in the developed world. Although many of the clinical features associated with such diseases have been determined, the contribution of genetic factors to these diseases remains uncertain.

Several gene variants that may modify the risk of heart attack have been identified, although the findings sometimes result in a relatively modest alteration to risk. In addition, genome-wide scans of families with MI have identified genomic regions which may contain gene(s) associated with the disease, although the specific gene location(s) have yet to be determined.

Research led by Kari Stefansson and colleagues at the Reykjavik-based firm deCODE Genetics have now identified two variants in the ALOX5AP gene, encoding the arachinodate 5-lipoxygenase-activating protein (FLAP), which may increase the risk of myocardial infarction or stroke.

The study was published online by Nature Genetics on 8 February 2004.

The researchers studied 713 Icelanders (in 296 families) who had suffered a heart attack and found that 29 per cent carried a variant of ALOX5AP (HapA). This variant was associated with an 80 per cent increase in heart attack risk; carriers of HapA may also be at a 67 per cent increase in the risk of stroke.

Although HapA was present in a UK population, the study failed to detect any association with MI risk. However, a second ALOX5AP variant (HapB) was shown to be associated with increased risk of heart attack among UK heart attack patients, although this association did not reach the same level of statistical significance as among Icelanders.

The ALOX5AP gene product, FLAP, has been implicated as playing a role in regulating the production of substances that trigger inflammation – such as leukotrienes, which are potent vasoconstrictors of coronary arteries. It is proposed that increased FLAP activity may lead to the accumulation of leukotrienes on fatty deposits on the arterial wall. The subsequent breakdown of these deposits by the immune system may then result in the development of blood clots and an increased risk of heart attack.

Adapted from an article by the Public Health Genetics Unit .

Further reading

Helgadottir A, et al. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet. 2004 Mar;36(3):233-9. Abstract