PHENOTYPE EXPRESSION IN FAMILIAL COMBINED HYPERLIPIDEMIA

Familial combined hyperlipidaemia (FCHL) is one of the most common her editary disorders predisposing to early coronary death. The affected f amily members have elevations of serum total cholesterol, triglyceride s or both. Despite intensive research efforts the genetic and metaboli c defects underlying this complex disorder are still unknown. To disse ct the metabolism and genetics of FCHL the phenotype of an individual must be precisely defined. We assessed the influence of different diag nostic criteria on the phenotype definition and studied factors affect ing the phenotype expression in 16 large Finnish families (n = 255) wi th FCHL. The fractile cut-points used to define abnormal lipid values had a profound influence on the diagnosis of FCHL. If the 90th percent ile cut-point was used, approximately 45% of the family members were a ffected, in concord with the presumed dominant mode of transmission fo r FCHL. If the 95th percentile was used only 22% of study subjects wer e affected. To characterize the metabolic differences or similarities between the different lipid phenotypes, we determined very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low densi ty lipoprotein (LDL) and high density lipoprotein (HDL) particles sepa rated by ultracentrifugation. In linkage analysis no single ultracentr ifugation variable could discriminate reliably affected family members from non-affected family members. Our data emphasizes the need for re -evaluation of FCHL diagnostic criteria. Preferably, the diagnosis sho uld be based on a single, reliable metabolic marker. (C) 1997 Elsevier Science Ireland Ltd.