title: Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is the most common form of irreversible blindness in developed countries. Variants in the factor H gene (CFH, also known as HF1), which encodes a major inhibitor of the alternative complement pathway, are associated with the risk for developing AMD. Here we test the hypothesis that variation in genes encoding other regulatory proteins of the same pathway is associated with AMD. We screened factor B (BF) and complement component 2 (C2) genes, located in the major histocompatibility complex class III region, for genetic variation in two independent cohorts comprising approximately 900 individuals with AMD and approximately 400 matched controls. Haplotype analyses identify a statistically significant common risk haplotype (H1) and two protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10), as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a significantly reduced risk of AMD (odds ratio = 0.45 and 0.36, respectively). Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% of the controls. These data expand and refine our understanding of the genetic risk for AMD.
authors.affiliation: Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702, USA.
authors.forename: Bert
authors.initials: B
authors.lastname: Gold
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Merriam
authors.forename: Jana
authors.initials: J
authors.lastname: Zernant
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Hancox
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Taiber
authors.forename: Karen
authors.initials: K
authors.lastname: Gehrs
authors.forename: Kevin
authors.initials: K
authors.lastname: Cramer
authors.forename: Julia
authors.initials: J
authors.lastname: Neel
authors.forename: Julie
authors.initials: J
authors.lastname: Bergeron
authors.forename: Gaetano R
authors.initials: GR
authors.lastname: Barile
authors.forename: R Theodore
authors.initials: RT
authors.lastname: Smith
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Hageman
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D003175:Complement C2 / Q000235:genetics*; D011415:Complement Factor B / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D008268:Macular Degeneration / Q000235:genetics*; D008969:Molecular Sequence Data
chemical_list: D003175:Complement C2; D011415:Complement Factor B