title: Association of MASP2 polymorphisms and protein levels with rheumatic fever and rheumatic heart disease.
abstract: MASP-2 is a key protein of the lectin pathway of complement system. Several MASP2 polymorphisms were associated with MASP-2 serum levels or functional activity. Here we investigated a possible association between MASP2 polymorphisms and MASP-2 serum levels with the susceptibility to rheumatic fever (RF) and rheumatic heart disease (RHD). We haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in 145 patients with history of RF from south Brazil (103 with RHD and 42 without cardiac lesion [RFo]) and 342 healthy controls. MASP-2 levels were determined by ELISA. The low MASP-2 producing p.377A and p.439H variants were negatively associated with RF (P=0.02, OR=0.36) and RHD (P=0.01, OR=0.25). In contrast, haplotypes that share the intron 9 - exon 12 g.1961795C, p.371D, p.377V and p.439R polymorphisms increased the susceptibility to RHD (P=0.02, OR=4.9). MASP-2 levels were associated with MASP2 haplotypes and were lower in patients (P<0.0001), which may reflect protein consumption due to complement activation. MASP2 gene polymorphisms and protein levels seem to play an important role in the development of RF and establishment of RHD.
authors.affiliation: Laboratório de Imunopatologia Molecular, Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: Sandra Jeremias dos Santos
authors.initials: SJ
authors.lastname: Catarino
authors.affiliation: Laboratório de Imunopatologia Molecular, Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil; Departamento de Genética, Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: Angelica Beate Winter
authors.initials: AB
authors.lastname: Boldt
authors.affiliation: Laboratório de Imunopatologia Molecular, Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: Marcia Holsbach
authors.initials: MH
authors.lastname: Beltrame
authors.affiliation: Laboratório de Imunopatologia Molecular, Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: Renato Mitsunori
authors.initials: RM
authors.lastname: Nisihara
authors.affiliation: Departamento de Medicina, Universidade Estadual de Ponta Grossa, Paraná, Brazil.
authors.forename: Marcelo Derbli
authors.initials: MD
authors.lastname: Schafranski
authors.affiliation: Laboratório de Imunopatologia Molecular, Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil. Electronic address: iarareason@hc.ufpr.br.
authors.forename: Iara Jose
authors.initials: IJ
authors.lastname: de Messias-Reason
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012213:Rheumatic Fever / Q000097:blood / Q000235:genetics*; D012214:Rheumatic Heart Disease / Q000097:blood / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases
keywords: Haplotype-specific genotyping; MASP2; Polymorphism; Rheumatic fever; Rheumatic heart disease