Apo B insertion/deletion polymorphisms are associated with atherosclerosis in young black but not young white males

Investigators in eight communities collected aortas, right coronary arteries, blood and liver samples, and associated information from 872 young males, aged 15-34 years, who died of external causes. Pathologists graded the arteries for atherosclerotic lesions, and a central laboratory measured lipoprotein cholesterol concentrations. Apolipoprotein (apo) B sequences were amplified in hepatic DNA samples to determine genotypes for length polymorphisms in the signal peptide of apo B. In addition to the insertion (ins) allele (27-amino acid signal peptide) and the deletion (del) allele (24 amino acids), we detected a rare allele (ins*) in whites with an in-frame insertion of two Leu codons in a region that normally contains six Leu codons. The frequency for the apo B del allele was lower in blacks than in whites (p<0.0001). In blacks, homozygotes for the ins allele had the lowest levels of serum cholesterol and very low plus low density lipoprotein cholesterol (VLDL+LDL-C), homozygotes for the del allele had the highest levels, and heterozygotes had intermediate levels (p=0.0509 for cholesterol, p=0.0530 for VLDL+LDL-C), but no differences were found in whites. In blacks, homozygotes for the ins allele had the least involvement of the thoracic and the abdominal aorta with lesions, homozygotes for the del allele had the greatest involvement, and heterozygotes had intermediate involvement (p=0.0328 for thoracic aorta, p=0.0104 for abdominal aorta), but no differences were found in whites. In blacks, apo B ins/del genotype accounted for 1.2% of the observed variation in lesions of the thoracic aorta and 1.7% of the variation in those of the abdominal aorta. The association of apo B ins/del genotypes with lesions in young blacks but not in young whites may contribute to explaining the excess of fatty streaks previously observed in young blacks.