Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration

Bert Gold; Joanna E Merriam; Jana Zernant; Lisa S Hancox; Andrew J Taiber; Karen Gehrs; Kevin Cramer; Julia Neel; Julie Bergeron; Gaetano R Barile; R Theodore Smith; Gregory S Hageman; Michael Dean; Rando Allikmets; AMD Genetics Clinical Study Group

doi:10.1038/ng1750

Back

Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration

Journal article

Open access

Peer reviewed

Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration

Bert Gold, Joanna E Merriam, Jana Zernant, Lisa S Hancox, Andrew J Taiber, Karen Gehrs, Kevin Cramer, Julia Neel, Julie Bergeron, Gaetano R Barile, …

Nature genetics, Vol.38(4), pp.458-462

04/2006

DOI: 10.1038/ng1750

PMCID: PMC2921703

PMID: 16518403

Files and links (1)

url

http://doi.org/10.1038/ng1750View

Open Access

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.

Haplotypes

Immunohistochemistry

Humans

Complement C2 - genetics

Molecular Sequence Data

Chromatography, High Pressure Liquid

Case-Control Studies

Complement Factor B - genetics

Macular Degeneration - genetics

Aged, 80 and over

Aging

Aged

Cohort Studies

Details

Title: Subtitle: Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration
Creators: Bert Gold - Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702, USA
Joanna E Merriam
Jana Zernant
Lisa S Hancox
Andrew J Taiber
Karen Gehrs
Kevin Cramer
Julia Neel
Julie Bergeron
Gaetano R Barile
R Theodore Smith
Gregory S Hageman
Michael Dean
Rando Allikmets
AMD Genetics Clinical Study Group
Resource Type: Journal article
Publication Details: Nature genetics, Vol.38(4), pp.458-462
DOI: 10.1038/ng1750
PMID: 16518403
PMCID: PMC2921703
NLM abbreviation: Nat Genet
ISSN: 1061-4036
eISSN: 1546-1718
Publisher: United States
Grant note: Intramural NIH HHS R01 EY015520-02 / NEI NIH HHS EY11515 / NEI NIH HHS R01 EY015520-03 / NEI NIH HHS R01 EY015520-04 / NEI NIH HHS R01 EY011515 / NEI NIH HHS N01-CO-124000 / NCI NIH HHS R01 EY015520-05 / NEI NIH HHS R01 EY015520 / NEI NIH HHS R01 EY015520-01A2 / NEI NIH HHS EY13435 / NEI NIH HHS R01 EY013435 / NEI NIH HHS
Language: English
Date published: 04/2006
Academic Unit: Microbiology and Immunology; Pathology; Ophthalmology and Visual Sciences
Record Identifier: 9983979908002771

Metrics

37 Record Views

912 Times Cited - Web of Science