title: Lack of evidence for linkage between low-density lipoprotein subclass phenotypes and the apolipoprotein B locus in familial combined hyperlipidemia.
abstract: Low-density lipoprotein (LDL) subclass phenotype B, characterized by a predominance of small, dense LDL particles, appears to be a genetically influenced risk factor for coronary heart disease. Phenotype B, as determined by gradient gel electrophoresis, appears to be inherited in a manner consistent with the presence of a single major genetic locus, based on complex segregation analysis. Familial combined hyperlipidemia (FCHL) is a disorder characterized by elevations in total plasma cholesterol and/or triglyceride levels in probands and family members, variable lipoprotein phenotypes over time, and elevations in apolipoprotein B levels. Because apo B is the primary protein component of LDL particles, the present study was undertaken to determine whether LDL subclass phenotypes are controlled by the APOB locus in FCHL families. The evidence against linkage was very strong based on lod score analyses (total lod = -13.3), under assumptions that LDL subclass phenotypes are influenced by a major genetic locus and that the mode of inheritance and penetrance functions are known. Other methods requiring fewer assumptions also provided evidence against linkage, although the strength of this evidence was weaker. Thus the results demonstrate that the proposed gene responsible for LDL subclass phenotypes is unlikely to be the APOB gene in families with FCHL.
authors.affiliation: Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle 98195.
authors.forename: M A
authors.initials: MA
authors.lastname: Austin
authors.forename: E
authors.initials: E
authors.lastname: Wijsman
authors.forename: S W
authors.initials: SW
authors.lastname: Guo
authors.forename: R M
authors.initials: RM
authors.lastname: Krauss
authors.forename: J D
authors.initials: JD
authors.lastname: Brunzell
authors.forename: S
authors.initials: S
authors.lastname: Deeb
mesh_terms: D000483:Alleles; D001055:Apolipoproteins B / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype
chemical_list: D001055:Apolipoproteins B; D008077:Lipoproteins, LDL