Beta2-glycoprotein I and its clinical significance: from gene sequence to protein levels.
In order to elucidate beta2-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 beta2-GPI literature was performed. The human beta2-GPI complete nucleotide sequence has been reported and it consists of 8 exons separated by large introns. The beta2-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 beta2-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 beta2-GPI promoter activity. Transcription factor binding sites for STAT, CREB, C/EBPbeta, NF-1, AP-1, NFAT, HNF-3beta and HNF-1 have been identified in the promoter region of the beta2-GPI gene by computer analysis. The beta2-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.
Sodin-Semrl
S
S
University Medical Centre, Division of Internal Medicine, Department of Rheumatology, Vodnikova 62, 1000 Ljubljana, Slovenia. snezna.sodin@kclj.si
Rozman
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D053482:beta 2-Glycoprotein I / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*
D053482:beta 2-Glycoprotein I