Genetics of serum lipoprotein disorders

In this paper a comprehensive review is presented of the literature on the diagnostic criteria, morbidity and mortality as well as effectiveness of treatment of familial hypercholesterolemia (FH), familial defective apolipoprotein B 100 (FDB), polygenic hypecholesterolemia (PH), familial hypertriglyceridemia, familial lipoprotein lipase deficiency, apolipoprotein C II deficiency, hepatic lipase deficiency, familial combined hyperlipidemia (FCH), type III hyperlipoproteinemia, abetalipoproteinemia, hypobetalipoproteinemia, Tangier disease, familial LCAT deficiency, fish-eye disease, cerebrotendinous xanthomatosis, cholesteryl ester storage disease,Wolman’s disease, Smith-Lemli-Opitz syndrome, familial cholesterol 7 alpha hydroxylase deficiency, familial hypoalphalipoproteinemia, familial hyperalphalipoproteinemia and sitosterolemia. Clinically the most important is FH which is the most common single-gene disorder. It is caused by mutations (to date over 700 have been reported) in the gene for the LDL receptors causing either reduction in the synthesis or the production of defective LDL receptors thus impairing their ability to bind, internalize and catabolize LDL particles. Therefore FH is characterized by raised serum total and LDL cholesterol concentrations that lead to premature fatal or non-fatal coronary heart disease (CHD). The high risk for early atherosclerosis and CHD in other severe familial hyperlipidemias, particularly in FDB, apo E2 homozygosity (remnant hyperlipidemia), PH and FCH is also stressed as well as the risk for pancreatitis due to hypertriglyceridemia in lipoprotein lipase and apo CII deficiency and familial hypertriglyceridemia.