[Mutagenic aspects of the lipoprotein lipase gene]

Lipoprotein lipase (LPL) is an enzyme involved in the metabolism of triglyceride-rich lipoproteins (chylomicrons and VLDL), participating also in the remodeling of HDL particles. It is encoded by a gene located on chromosome 8 (8p22), containing 10 exons. Abnormalities in this gene lead to the development of LPL enzyme deficiency. About 100 mutations have been described in the LPL gene, the most frequent being Asp9Asn, Gly188Glu and Asn291Ser. Mutations in the homozygous form are associated with type I hyperlipoproteinemia (familial chylomicronemia). Mutations in the heterozygous state have a significant incidence in population (3-7%) and lead to a decrease in the LPL activity with up to 50%, which causes the modification of the plasma lipid profile, meaning an increase in triglycerides and a decrease in HDL cholesterol. Both modifications represent cardiovascular risk factors, so that the carriers of LPL gene mutations have an increased predisposition to develop coronary heart disease. Moreover, the association of heterozygous mutations in the LPL gene in individuals with genetic-type hyperlipoproteinemias may aggravate the perturbations of the lipid profile and, consequently, they can increase the cardiovascular risk in these patients. The accumulated data may be considered an argument for the importance of investigating LPL gene mutations in the population, in order to detect precociously the individuals with an increased atherogenic predisposition and to decide on the appropriate therapy.