A la recherche des genes athérogénes: I’exemple de la lipoprotéine(a)

Identifying a genetic predisposition to atherosclerosis: the example of lipoprotein(a) Coronary artery disease results from strong gene-environment interactions. The genetic basis of this disease is complex and polygenic. The present review summarises the methods used to identify genes associated with heart disease, it describes briefly our work on apo(a) and emphasises the importance of family history to identify a genetic predisposition to coronary heart disease. Apo(a), the distinctive glycoprotein of lipoprotein(a) [Lp(a)], is a candidate gene for atherosclerosis. Indeed, elevated plasma concentrations of Lp(a) are mostly due to specific sequence variations within the apo(a) gene and are associated with premature atherosclerosis. Over the last years, our laboratory has investigated the impact of various clinical situations on the metabolism of Lp(a), and has observed large and unexpected variations in plasma concentrations of Lp(a) in renal disease, in HIV-infection and in sepsis. Moreover, we have recently identified an association between apo(a) and Alzheimer disease. As such, our observations suggest apo(a) may constitute an innovative target in our fight against cardiovascular and neurodegenerative disorders.