Genetic dissection of familial combined hyperlipidemia

Familial combined hyperlipidemia (FCHL) is the most common genetic hyperlip idemia in man. FCHL is characterized by familial clustering of hyperlipidem ia and clinical manifestations of premature coronary heart disease, i.e., b efore the age of 60. Although FCHL was delineated about 25 years ago, at pr esent the FCHL phenotype and its complex genetics are not fully understood. Initially, the familial aggregation of high plasma total cholesterol and t riglyceride levels, with a bimodal distribution of triglycerides, was taken as evidence of a dominant mode of inheritance. However, it is now clear th at the genetics of FCHL is more complex, and it has been suggested that FCH L is heterogeneous. Several approaches can be taken to identify genes contr ibuting to the disease phenotype in complex genetic disorders either by stu dying the disease in the human situation or by using animal models. Recent reports have shown that a combination of genetic linkage studies, associati on studies, and differential gene expression studies provides a useful tool for the genetic dissection of complex diseases. Therefore, the genetic str ategies that will be used to dissect the genetic background of FCHL are rev iewed. (C) 2001 Academic Press.