β2-Glycoprotein I and its clinical significance: From gene sequence to protein levels

In order to elucidate β2-GPI at the DNA level and characterize its polymorphisms, mRNA expression, protein levels and clinical significance at each of these steps, a molecular review of β2-GPI literature was performed. The human β2-GPI complete nucleotide sequence has been reported and it consists of 8 exons separated by large introns. The β2-GPI gene is polymorphic with four alleles. The distribution of point mutations can be significantly different between various racial populations. DNA variation studies of the β2-GPI gene identified a total of 151 single-nucleotide polymorphisms, 26 of which are within regions with potential clinical significance. Southern blot analysis indicated the presence of one gene product only. An atypical TATA box and a hepatic nuclear factor-1 element are both essential for β2-GPI promoter activity. Transcription factor binding sites for STAT, CREB, C/EBPβ, NF-1, AP-1, NFAT, HNF-3β and HNF-1 have been identified in the promoter region of the β2-GPI gene by computer analysis. The β2-GPI transcriptional signal of 1.5 kb was detected in Northern blot analysis and its 326-amino-acid sequence was found to be one of the most proline-rich eukaryotic proteins. Amino acid substitutions have been shown to be associated with loss of phospholipid binding, development and recognition of antiphospholipid antibodies.