The atherogenic lipoprotein phenotype (ALP) is a common heritable trait characterized by a preponderance of small, dense low density lipoprotein (LDL) particles (subclass pattern B), increased levels of triglyceride-rich lipoproteins, reduction in high density lipoprotein, and a 3-fold ... The atherogenic lipoprotein phenotype (ALP) is a common heritable trait characterized by a preponderance of small, dense low density lipoprotein (LDL) particles (subclass pattern B), increased levels of triglyceride-rich lipoproteins, reduction in high density lipoprotein, and a 3-fold increased risk of myocardial infarction (summary by Nishina et al., 1992). The so-called atherogenic lipoprotein phenotype was shown by Austin et al. (1988) to be independently associated with an increased risk for coronary artery disease. Allayee et al. (1998) concluded, furthermore, that there is a genetically based association between familial combined hyperlipidemia (FCHL; 144250) and small, dense LDL particles and that the genetic determinants for LDL particle size are shared, at least in part, among FCHL families and the more general population at risk for coronary artery disease. Juo et al. (1998) concluded from a bivariate segregation analysis of small, dense LDL particles and elevated apolipoprotein B levels (APOB; 107730), which are commonly found together in members of FCHL families, that the 2 traits share a common major gene plus individual polygenic components. The common major gene was estimated to explain 37% of the variance of adjusted LDL particle size and 23% of the variance of adjusted apoB levels.
Naggert et al.(1997) followed up on the family study showing tight linkage of the atherogenic lipoprotein phenotype to the LDL receptor locus (LDLR; 606945) on 19p13.2. To test whether a mutation in the structural portion of the LDLR ... Naggert et al.(1997) followed up on the family study showing tight linkage of the atherogenic lipoprotein phenotype to the LDL receptor locus (LDLR; 606945) on 19p13.2. To test whether a mutation in the structural portion of the LDLR gene could be responsible for the phenotype, they sequenced the exons of the receptor-binding domain for each pair of parents in the 11 pedigrees. For the remaining 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 found. They concluded that a mutant allele of LDLR is not likely to be responsible for ALP.