title: Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn's Disease Patients.
abstract: Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti-Saccharomyces cerevisiae antibody levels is observed in Crohn's disease and this deficiency is frequently associated with a severe Crohn's disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn's disease phenotype in 69 Crohn's disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn's disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn's disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants.
authors.affiliation: INSERM, U995, F-59000 Lille, France.|University Lille2, U995-LIRIC, Lille Inflammation Research International Centre, F-59000 Lille, France.|CHU Lille, Service de Parasitologie Mycologie, Pôle de Biologie Pathologie Génétique, F-59000 Lille, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Choteau
authors.affiliation: Université Lille Nord de France, Unité de Biostatistique, EA 2694, F-59000 Lille, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Vasseur
authors.affiliation: Genetic platform, F-59000 Lille, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Lepretre
authors.affiliation: Genetic platform, F-59000 Lille, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.affiliation: INSERM, U995, F-59000 Lille, France.|University Lille2, U995-LIRIC, Lille Inflammation Research International Centre, F-59000 Lille, France.
authors.forename: Corine
authors.initials: C
authors.lastname: Gower-Rousseau
authors.affiliation: INSERM, U995, F-59000 Lille, France.|University Lille2, U995-LIRIC, Lille Inflammation Research International Centre, F-59000 Lille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Dubuquoy
authors.affiliation: INSERM, U995, F-59000 Lille, France.|University Lille2, U995-LIRIC, Lille Inflammation Research International Centre, F-59000 Lille, France.|CHU Lille, Service de Parasitologie Mycologie, Pôle de Biologie Pathologie Génétique, F-59000 Lille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Poulain
authors.affiliation: Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: INSERM, U995, F-59000 Lille, France.|University Lille2, U995-LIRIC, Lille Inflammation Research International Centre, F-59000 Lille, France.|CHU Lille, Service de Parasitologie Mycologie, Pôle de Biologie Pathologie Génétique, F-59000 Lille, France.
authors.forename: Boualem
authors.initials: B
authors.lastname: Sendid
authors.affiliation: INSERM, U995, F-59000 Lille, France.|University Lille2, U995-LIRIC, Lille Inflammation Research International Centre, F-59000 Lille, France.|CHU Lille, Service de Parasitologie Mycologie, Pôle de Biologie Pathologie Génétique, F-59000 Lille, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Jawhara
mesh_terms: D003424:Crohn Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D053589:Nuchal Cord; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012441:Saccharomyces cerevisiae / Q000276:immunology
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C084067:MASP1 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases