Genetic dyslipidemias

Although genetic factors strongly influence lipid metabolism, genetic dyslipidemias refer to specific monogenic defects that significantly alter the function of proteins involved in lipid metabolism. Familial hypercholesterolemia results from mutations in the genes coding for LDL-receptor, apolipoprotein B100 (apoB100), PCSK9, or LDLRAP1. The rare homozygous form is severe, with extravascular lipid deposits at an early age and a high incidence of coronary events in childhood, in the absence of early diagnosis. The heterozygous form is more frequent and characterized by elevated plasma LDL-cholesterol levels (>190mg/dL in adults) and a very high risk of premature coronary artery disease (usually before the age of 50years). Familial chylomicronemia syndrome (FCS) is a major form of genetic hypertriglyceridemia caused by mutations in genes encoding lipoprotein lipase or one of its cofactors (apoC-II, apoA-V, GPIHBP1, or LMF1). Patients with FCS exhibit markedly elevated plasma triglyceride levels (>10mmol/L) and are at high risk for acute pancreatitis. Congenital familial partial lipodystrophy and glycogen storage diseases are two other forms of genetic hypertriglyceridemia. In addition, other rare genetic dyslipidemias have been described in humans, including familial dysbetalipoproteinemia, abetalipoproteinemia, familial hypobetalipoproteinemia, familial combined hypolipidemia, sitosterolemia, and hypoalphalipoproteinemias.