Cardiovascular disease (CVD) arises as a result of genetic predisposition in the context of a disease-promoting environment.

While several risk factors have been identified for CVD, such as elevated serum lipid levels and hypertension, most of the genes identified thus far do not appear to involve such 'conventional' risk factors.

Moreover, the interactions between genes and environment, such as a diet high in certain fats, adds another level of complexity to CVD and renders identification of the underlying genetic factors even more difficult.

Polyunsaturated fatty acids (PUFAs), such as the omega-6 and omega-3 fatty acids, which have multiple roles in membrane structure, lipid metabolism, blood clotting, blood pressure, and, in particular, inflammation, have been linked to the reduction in CVD.

Linoleic (omega-6) and alpha-linolenic acid (omega-3) are essential fatty acids that can be converted into long-chain PUFAs, such as arachidonic acid (AA) and eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA), respectively.

These long-chain PUFAs are metabolized by enzymatically catalyzed systems via cyclooxygenases and lipoxygenases. The 5-lipoxygenase (5-LO)/leukotriene (LT) biosynthesis pathway has been biochemically and genetically associated with CVD traits in mice and humans, particularly in the context of dietary AA and EPA/DHA.

In this review, we summarize the biochemical metabolism of omega-3 and omega-6 PUFAs, evaluate the evidence for genetic and nutrigenetic contributions of 5-LO pathway genes to CVD, and discuss the potential of future studies that could identify other gene-dietary interactions between PUFAs and CVD traits.