Linkage analysis of low‐density lipoprotein subclass phenotypes and the apolipoprotein B gene

A common heritable phenotype has recently been identified which is characterized by a relative abundance of small, dense low-density lipoproteins (LDL), and mild elevations of plasma triglycerides and reductions in plasma high-density lipoproteins (HDL) cholesterol. This phenotype, designated LDL subclass phenotype B, has been associated with up to a three-fold increase in coronary disease risk. Complex segregation analysis in two large family studies has demonstrated that LDL subclass phenotype B is influenced by an allele at a single genetic locus with a population frequency of 0.25-0.3, and autosomal dominant inheritance, but with full penetrance only in males age 20 and over and in postmenopausal women. Since apolipoprotein B (apoB) is the principal protein component of LDL, linkage analysis was used to investigate possible linkage between the phenotype B phenotype and the apoB gene, using a variable number of tandem repeats site located 0.5 kb from the 3' end of the apoB gene. In 6 informative families including only family members in the penetrant classes, a total LOD score of -7.49 was found at a recombination fraction of 0.001. Thus, under the assumptions of the single gene model, it is unlikely that the apoB locus controls LDL subclass phenotype B.