title: Novel MASP2 variants detected among North African and Sub-Saharan individuals.
abstract: The lectin pathway of the complement system is activated when mannan-binding lectin (MBL) in complex with MBL-associated serine protease 2 (MASP-2) binds to carbohydrate structures on microorganisms. Structural gene mutations and promoter polymorphisms in the MBL2 gene responsible for low-MBL serum levels are present in all human populations and associate with increased risk of infection. Recently, investigations on Danes revealed the existence of a mutation on the MASP2 gene, which introduces an amino acid substitution in the CUB1 domain (Asp105Gly; numbering refers to the mature protein), and is associated with reduction in the level of MASP-2 in serum. Here, we present the results of a sequence-based typing analysis of the MBL2 and MASP2 gene polymorphisms in a group of 65 Africans (50 North Africans and 15 Sub-Saharan) and of 104 Spaniards. The analysis identified three novel exon 3 MASP2 variants introducing amino acid substitutions at positions 84 (Arg-->Gln), 103 (Arg-->Cys) and 111 (Pro-->Leu) in the CUB1 domain. None of these variants were identified in Spaniards. The Arg84Gln was detected in four of the 15 Sub-Saharans. The Arg103Cys and Pro111Leu variants were detected only among North Africans (two and four individuals, respectively). The Asp105Gly variant was similarly represented among Spaniards and North Africans (three and two individuals, respectively), which appears to be a lower frequency than that reported for Danes (5.5%). As reported for MBL2, the marked geographic distribution of the new MASP2 variants may represent an evolutionary adaptation to different environments.
authors: Servei d'Immunologia, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. lozano@ub.edu
authors: F
authors: F
authors: Lozano
authors: B
authors: B
authors: Suárez
authors: A
authors: A
authors: Muñoz
authors: J C
authors: JC
authors: Jensenius
authors: J
authors: J
authors: Mensa
authors: J
authors: J
authors: Vives
authors: J-P
authors: JP
authors: Horcajada
mesh_terms: D017954:Africa South of the Sahara; D000352:Africa, Northern; D000595:Amino Acid Sequence; D001483:Base Sequence; D015331:Cohort Studies; D003181:Complement C4 / Q000032:analysis / Q000235:genetics; D037582:Complement Pathway, Mannose-Binding Lectin / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D037601:Mannose-Binding Lectin / Q000032:analysis / Q000235:genetics; D050606:Mannose-Binding Protein-Associated Serine Proteases; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics*; D013030:Spain
chemical_list: D003181:Complement C4; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases