THE ATHEROGENIC LIPOPROTEIN PHENOTYPE IS NOT CAUSED BY A MUTATION IN THE CODING REGION OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE

The atherogenic lipoprotein phenotype (ALP) is a common heritable trai t characterized by a predominance of small, dense low density lipoprot ein particles (subclass pattern B), increased levels of triglyceride-r ich lipoproteins, reductions in high density lipoproteins, and an incr eased risk for myocardial infarction. In a previous linkage study of 1 1 families, evidence for tight linkage of subclass pattern B with the LDL receptor (LDLR) locus on chromosome 19p13.2 was obtained. To test whether a mutation in the structural portion of the LDLR gene could be responsible for the phenotype, we first sequenced the exons of the re ceptor binding domain for each pair of parents in these 11 pedigrees. For the remaining portion of the LDLR coding region, exons as well as cloned LDLR cDNAs were sequenced for selected members of the pedigrees . No mutations that changed the amino acid sequence of the LDLR were f ound. We conclude that it is unlikely that a mutant allele of the LDLR protein is responsible for ALP.