title: A novel mannose-binding lectin-associated serine protease 1/3 gene variant.
abstract: The ficolins and mannose-binding lectin (MBL) create complexes with three different serine proteases (MASP-1, MASP-2 and MASP-3) and a truncated non-enzymatic form of MASP-2 (sMAP). MASP-2 is able to activate complement by cleavage of C4 and C2, while the physiological functions of MASP-1, MASP-3 and sMAP still are debated. MASP-1 and MASP-3 are alternative spliced forms of the same MASP gene. To gain insight in the molecular variation in the MASP-1/3 gene, we undertook a systematic study of the protein coding sequences of the MASP-1/3 gene. The coding regions of the MASP-1/3 gene were sequenced in 92 healthy Caucasian donors. A total of six nucleotide substitutions were detected. Five were detected only once. One polymorphism identified in exon 10 at position +50074 (rs 38343199) relative to the transcription start site resulting in the amino acid substitution of a glycine (GGG) with a glutamic acid residue (GAG) in the second complement control protein domain was observed. The frequency of this allele in 305 blood donors, 90 patients with systemic lupus erythematosus and 234 patients with the systemic inflammatory response syndrome (SIRS) and/or sepsis was 0.03, 0.017 and 0.03 respectively. No significant differences in genotype frequencies between the groups were observed (P > 0.45). However, the SIRS/sepsis group deviated from the Hardy-Weinberg expectations due to one variant allele homozygote (P = 0.07), which was not observed in the other groups. In conclusion, the MASP1/3 gene harbours a low-frequent polymorphic site resulting in an amino acid substitution, which may influence the function of the gene product.
authors: Tissue Typing Laboratory-7631, Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: G
authors: G
authors: Weiss
authors: H O
authors: HO
authors: Madsen
authors: P
authors: P
authors: Garred
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D014644:Genetic Variation; D018698:Glutamic Acid / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics*; D011110:Polymorphism, Genetic; D018805:Sepsis / Q000235:genetics / Q000276:immunology; D013577:Syndrome
chemical_list: D018698:Glutamic Acid; C084067:MASP1 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases; D005998:Glycine