Dyslipidemia is a commonly encountered clinical condition and is an important 
determinant of cardiovascular disease. Although secondary factors play a role in 
clinical expression, dyslipidemias have a strong genetic component. Familial 
hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the 
gene coding for low density lipoprotein receptor and genes encoding for proteins 
that interact with the receptor: APOB, PCSK9 and LDLRAP1. Monogenic 
hypertriglyceridemia is the result of mutations in genes that regulate the 
metabolism of triglyceride rich lipoproteins (eg LPL, APOC2, APOA5, LMF1, 
GPIHBP1). Conversely familial hypobetalipoproteinemia is caused by inactivation 
of the PCSK9 gene which increases the number of LDL receptors and decreases 
plasma cholesterol. Mutations in the genes APOB, and ANGPTL3 and ANGPTL4 (that 
encode angiopoietin-like proteins which inhibit lipoprotein lipase activity) can 
further cause low levels of apoB containing lipoproteins. Abetalipoproteinemia 
and chylomicron retention disease are due to mutations in the microsomal 
transfer protein and Sar1b-GTPase genes, which affect the secretion of apoB 
containing lipoproteins. Dysbetalipoproteinemia stems from dysfunctional apoE 
and is characterized by the accumulation of remnants of chylomicrons and very 
low density lipoproteins. ApoE deficiency can cause a similar phenotype or 
rarely mutations in apoE can be associated with lipoprotein glomerulopathy. Low 
HDL can result from mutations in a number of genes regulating HDL production or 
catabolism; apoAI, lecithin: cholesterol acyltransferase and the ATP-binding 
cassette transporter ABCA1. Patients with cholesteryl ester transfer protein 
deficiency have markedly increased HDL cholesterol. Both common and rare genetic 
variants contribute to susceptibility to dyslipidemias. In contrast to rare 
familial syndromes, in most patients, dyslipidemias have a complex genetic 
etiology consisting of multiple genetic variants as established by genome wide 
association studies. Secondary factors, obesity, metabolic syndrome, diabetes, 
renal disease, estrogen and antipsychotics can increase the likelihood of 
clinical presentation of an individual with predisposed genetic susceptibility 
to hyperlipoproteinemia. The genetic profiles studied are far from complete and 
there is room for further characterization of genes influencing lipid levels. 
Genetic assessment can help identify patients at risk for developing 
dyslipidemias and for treatment decisions based on 'risk allele' profiles. This 
review will present the current information on the genetics and pathophysiology 
of disorders that cause dyslipidemias.