Familial combined hyperlipidemia and insulin resistance : distant relatives linked by intra-abdominal fat?

Familial combined hyperlipidemia (FCHL), originally identified by Goldstein et al,1 Rose et al,2 and Nikkila et al3 in the early 1970s, is a metabolic defect in lipoprotein metabolism that is associated with a predominance of small, dense LDL particles and appears to be a consequence of hepatic overproduction of apolipoprotein B-100 (apoB-100). Characteristic lipoprotein abnormalities include increases in apoB with variable manifestations of hyperlipidemia, including hypertriglyceridemia and/or increases in LDL cholesterol. Although FCHL has historically been viewed as a monogenic disorder, more recent analyses suggest that the disorder may be predicted by a threshold model in which apoB level genotype and LDL subclass phenotype interact to increase the risk of FCHL.4 Despite the fact that FCHL appears to be the most common genetic cause of hyperlipidemia and almost certainly predisposes to more coronary heart disease (CHD) events than any other known genetic disorder, the mechanism for increases in hepatic overproduction of apoB-containing lipoproteins remains unclear. Moreover, although genes have been identified that may contribute to the dyslipidemia of FCHL,5 a genetic explanation for the increases in apoB production is lacking.