The human apolipoprotein B 3' hypervariable region: detection of eight new alleles and comparisons of allele frequencies in blacks and whites.

We investigated common length polymorphisms in the hypervariable region located 3' to the human gene encoding apolipoprotein B (APOB 3' HVR) as part of the "Pathobiological Determinants of Atherosclerosis in Youth (PDAY)" study. PDAY is a multicenter study of young persons who died of external causes (accident, homicide, and suicide). The APOB 3' HVR contains multiple copies of AT-rich tandem repeats (15bp) called hypervariable elements (HVE). Using polymerase chain reaction (PCR) to amplify APOB sequences in hepatic DNA samples, we identified 22 different HVR alleles among 232 PDAY cases. In addition to 14 previously identified alleles, we detected 8 new alleles that had not been observed in population surveys. Of these new alleles, 7 were present only in black cases. We also examined distributions of HVR allele frequencies for blacks and whites. The frequency distributions for whites did not differ from those from previous studies of French populations (P = 0.3811) and Austrian populations (P = 0.1885). In contrast, the allele frequency distribution for blacks differed from whites (P < 0.001). Blacks had higher frequencies of smaller alleles (< or = 33 repeats) and larger alleles (> or = 37 repeats) than whites. We also sequenced specific HVR alleles to identify differences responsible for size variation. The most frequent alleles were identical in sequence to HVR alleles described in previous studies. However, one allele was not identical in sequence to an equivalent-sized allele from a previous study. In all likelihood, detection of sequence substitutions in the APOB 3' HVR would result in an even greater amount of allelic variability than detected by size differences alone.