Chimpanzee apolipoprotein H (beta(2)-glycoprotein I): report on the gene structure, a common polymorphism, and a high prevalence of antiphospholipid antibodies

Apolipoprotein H (apoH, protein; APOH, gene) is a 50-kDa glycoprotein that binds to negatively charged substrates, including phospholipids. ApoH is a main target antigen for the binding of antiphospholipid antibodies that are associated with thrombotic events. We have previously characterized the st ructural organization of the human APOH gene. Because of the significant st ructural homology between the human and chimpanzee genomes, we have employe d oligonucleotides from the human APOH gene sequence to amplify chimpanzee DNA covering the entire transcribed region together with flanking sequence in the 5' region. As in humans, the chimpanzee APOH gene consists of eight exons and seven introns and encodes for a 326-amino-acid protein. The deduc ed amino acid and nucleotide sequence show 99.4% and 99.6% similarity betwe en human and chimpanzee APOH, respectively. Using isoelectric focusing (IEF ) and immunoblotting, we screened 155 chimpanzees (128 unrelated captured p arents and 27 captive-born offspring) for the apoH protein polymorphism. Th e most common IEF pattern in chimpanzees was identical to a previously desc ribed APOH*3 allele in humans. In addition, an anodally shifted pattern was observed in chimpanzees with an allele frequency of 0.168, and the corresp onding allele was designated as APOH*4. DNA sequencing of APOH*4 carriers r evealed a missense mutation in exon 6 (A--->G) at codon 210, which replaces the amino acid lysine by glutamic acid. This mutation does not affect the binding of apoH to cardiolipin as revealed by cardiolipin/enzyme-linked imm unosorbent assay (ELISA). We also evaluated the prevalence of anti-apoH ant ibodies in chimpanzee plasma by using human-apoH-based ELISA and the associ ation of the Lys210Glu mutation with the occurrence of anti-apoH antibodies . The prevalence of anti-apoH antibodies in chimpanzees (64%) was found to be unusually high compared with that found in humans. However, the Lys210Gl u mutation showed no association with the occurrence of anti-apoH antibodie s. The prevalence of anti-apoH antibodies in chimpanzees may serve as a use ful animal model for the human antiphospholipid syndrome, where these antib odies are associated with clinical manifestations.