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 phenotyope 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.