title: Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients.
abstract: Genes of innate immunity may be involved in early onset of chronic Pa (Pseudomonas aeruginosa) colonization (cPaC) in cystic fibrosis (CF) patients. We studied 19 single nucleotide polymorphisms (SNPs) in 5 genes coding for proteins of the lectin complement pathway: MBL2 (Mannose binding lectin 2), MASP 1, 2, 3 (MBL-associated serine Protease) and FCN 1, 2 (Ficolin) gene in 96 CF patients. Association survival analysis using different genetic models was performed looking for an association between SNPs and age at onset of cPaC. CF patients who are MBL deficient are earlier chronic Pa colonized compared to MBL sufficient patients. Also patients with MBL2 genotype YO/YO, YO/XA, XA/XA, YA/YO and YA/XA are earlier chronic Pa colonized. CF patients heterozygous or homozygous for mutant alleles of two linked SNPs in the FCN1 gene (rs2989727 and rs1071583) are earlier colonized with Pa. Similarly, earlier onset of Pa colonization is seen in CF patients heterozygous for linked SNPs of FCN2 gene (rs7865453 and rs7851696) and MASP3 gene (rs7851696). Variants in MBL2, FCN1, FCN2 and MASP3 genes are significantly associated with earlier onset of chronic P. aeruginosa colonization.
authors.affiliation: Department of Pediatric Pulmonology and Immunology, Ghent University Hospital Ghent, Gent, Belgium. filomeen.haerynck@ugent.be
authors.forename: F
authors.initials: F
authors.lastname: Haerynck
authors.forename: K
authors.initials: K
authors.lastname: Van Steen
authors.forename: T
authors.initials: T
authors.lastname: Cattaert
authors.forename: B
authors.initials: B
authors.lastname: Loeys
authors.forename: S
authors.initials: S
authors.lastname: Van Daele
authors.forename: P
authors.initials: P
authors.lastname: Schelstraete
authors.forename: K
authors.initials: K
authors.lastname: Claes
authors.forename: M
authors.initials: M
authors.lastname: Van Thielen
authors.forename: I
authors.initials: I
authors.lastname: De Canck
authors.forename: J M
authors.initials: JM
authors.lastname: Mahachie John
authors.forename: F
authors.initials: F
authors.lastname: De Baets
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D037582:Complement Pathway, Mannose-Binding Lectin / Q000235:genetics* / Q000276:immunology; D003550:Cystic Fibrosis / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D005260:Female; D005838:Genotype; D006801:Humans; D037102:Lectins / Q000235:genetics; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D055815:Young Adult; D000097604:Ficolins
chemical_list: D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins; C445619:MBL2 protein, human; C084067:MASP1 protein, human