title: Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study.
abstract: BACKGROUND
  In age-related macular degeneration (AMD) the complement system is thought to be activated by chronic oxidative damage with genetic variants identified in the alternative pathway as susceptibility factors. However, the involvement of the lectin pathway of complement, a key mediator of oxidative damage, is controversial. This study investigated whether mannose-binding lectin (MBL) levels and genetic variants in lectin pathway proteins, are associated with the predisposition to and severity of AMD.
  
  
  METHODS
  MBL levels and single nucleotide polymorphisms (SNPs) in the MBL2 and the ficolin-2 (FCN2) gene were determined in 109 patients with AMD and 109 age- and sex-matched controls.
  
  
  RESULTS
  MBL expression levels were equally distributed in both cases (early and late AMD) and controls (p>0.05). However, there was a trend towards higher median MBL levels in cases with late AMD compared to cases with early AMD (1.0 vs. 0.4 μg/ml, p = 0.09) and MBL deficiency (<0.5 μg/ml) was encountered less frequently in the late AMD group (35% vs 56%, p = 0.03). FCN2 and MBL2 allele frequencies were similarly distributed in early and late AMD cases compared with controls (p>0.05 for all analyses) as were MBL2 genotypes. Similarly, there was no significant difference in allele frequencies in any SNPs in either the MBL2 or FCN2 gene in cases with early vs. late AMD.
  
  
  CONCLUSIONS
  SNPs of lectin pathway proteins investigated in this study were not associated with AMD or AMD severity. However, MBL levels deserve further study in a larger cohort of early vs. late AMD patients to elucidate any real effect on AMD severity.
authors.affiliation: Victorian Infectious Diseases Service at the Doherty Institute, Melbourne Health, Melbourne, Victoria, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Osthoff
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Kelvin Grove, Queensland, Australia.
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Dean
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Richardson
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Daniell
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
authors.affiliation: Victorian Infectious Diseases Service at the Doherty Institute, Melbourne Health, Melbourne, Victoria, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Damon P
authors.initials: DP
authors.lastname: Eisen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D037102:Lectins / Q000097:blood / Q000235:genetics*; D008268:Macular Degeneration / Q000097:blood / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000097604:Ficolins
chemical_list: D037102:Lectins; D037601:Mannose-Binding Lectin; D000097604:Ficolins; C445619:MBL2 protein, human