HDL genetics: candidate genes, genome wide scans and gene-environment interactions.

Cardiovascular disease (CVD) is multifactorial and its manifestation is determined by interactions among genes, as well as among genetic factors and numerous environmental factors. It has long been known that low levels of high density lipoprotein cholesterol (HDL-C) are associated with increased CVD risk. Moreover, the emerging data from developing countries, suggest that this may be the most common lipid abnormality observed in those societies. It has been clearly demonstrated that variation at several candidate genes has a significant effect over the spectrum of HDL-C levels observed in the general population. In addition, these effects are modulated by several non-modifiable such as gender and age, and modifiable factors, such as diet, smoking, obesity, and alcohol intake among many others. The lessons that we are learning from studying candidate gene-environment interactions should help us to chart the intricacies of the biochemical pathways involved in lipoprotein metabolism. Moreover, similar models need to be applied to the analysis of genome wide searches aimed to uncover new genes involved in HDL metabolism and reverse cholesterol transport. This knowledge should facilitate more targeted and effective public health policies, especially in developing countries, where the fast environmental changes are modifying the disease patterns by exposing a large number of susceptible individuals to the factors that have been responsible for the high prevalence of CVD in Western industrialized countries.