The Inheritance of low density lipoprotein (LDL) subclass patterns was Investigated In 234 members of seven large kindreds with familial combined hyperlipidemia (FCHL), a disorder characterized by elevated LDL cholesterol and/or trlglyceride and Increased coronary disease risk in families. Analysis of LDL subclasses by nondenaturlng gradient gel electrophoresls showed a predominance of large, buoyant LDL particles (pattern A) In 71% of the family members and a predominance of small, dense LDL particles (pattern B) In 29% of family members. Based on complex segregation analysis, pattern B appeared to be Inherited as an autosomal trait with either a dominant or an additive mode of Inheritance and a small, but significant, multlfactorlal inheritance component The proposed allele for pattern B was common (frequency=0.3), and reduced penetrance was observed among men under age 20 and among women under age 50. These results In these FCHL families are consistent with those from a previously reported population-based sample of families, In which pattern B showed an apparent dominant mode of Inheritance. In that study, reduced penetrance was observed for men under age 20 and for premenopausal women, but a somewhat lower allele frequency was found for pattern B (0.25). In the FCHL family members, LDL subclass pattern B was associated with significantly increased plasma levels of apolipoproteln B and trlglyceride and decreased high density lipoprotein cholesterol. In comparison with a group of controls, the FCHL family members with pattern A had similar mean trlglyceride levels, but higher mean apolipoproteln B. Thus, In families with FCHL, a predominance of small, dense LDL particles appears to be Inherited as a common, single-gene trait, which Is closely associated with the higher plasma trlglyceride levels found In these families. The Increased plasma apolipoproteln B levels found In FCHL cannot, however, be accounted for by this proposed locus.
Arteriosclerosis – Wolters Kluwer Health
Published: Jul 1, 1990