Major locus inheritance of apolipoprotein B in Utah pedigrees.

A major locus that determines levels of apolipoprotein B (apoB) was revealed by likelihood analysis on 331 members of 36 pedigrees. The major locus explained 43.2% of the observed variance, with the remainder attributed to random environmental factors. Estimated mean apoB levels (mg/dl) were 110.5 +/- 2.5, 141.9 +/- 4.4, and 208.1 +/- 11.5 for low homozygotes, heterozygotes, and high homozygotes, respectively. The corresponding genotypic frequencies were 0.718, 0.259, and 0.023. The apoB locus explained 13% and 14% of the variance in total and low-density-lipoprotein cholesterol levels, respectively. Persons with elevated apoB had normal to high levels of total serum cholesterol and triglyceride and low to normal levels of high-density lipoprotein and apolipoprotein A-I. Sixteen members of three of the pedigrees were heterozygous for familial hypercholesterolemia (FH). Their apoB levels were estimated as 35.72 +/- 7.16 mg/dl above the apoB genotypic means, assuming that the two loci act independently. Therefore, two major loci, the FH locus and the apoB locus, affect two levels, apoB and LDL cholesterol.