April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
A Common SNP at the CFI Locus is Associated with Rapid Progression of Geographic Atrophy
Author Affiliations & Notes
  • Brian Yaspan
    Genentech, Inc., South San Francisco, CA
  • Zhengrong Li
    Genentech, Inc., South San Francisco, CA
  • Amy Dressen
    Genentech, Inc., South San Francisco, CA
  • Menno van Lookeren Campagne
    Genentech, Inc., South San Francisco, CA
  • Robert R Graham
    Genentech, Inc., South San Francisco, CA
  • Kha Le
    Genentech, Inc., South San Francisco, CA
  • Tushar Bhangale
    Genentech, Inc., South San Francisco, CA
  • Phillip Lai
    Genentech, Inc., South San Francisco, CA
  • Carole Ho
    Genentech, Inc., South San Francisco, CA
  • Eric C Strauss
    Genentech, Inc., South San Francisco, CA
  • Footnotes
    Commercial Relationships Brian Yaspan, Genentech, Inc. (E), Roche (I); Zhengrong Li, Genentech, Inc. (E), Roche (I); Amy Dressen, Genentech, Inc. (E), Roche (I); Menno van Lookeren Campagne, Genentech, Inc. (E), Roche (I); Robert Graham, Genentech, Inc. (E), Roche (I); Kha Le, Genentech, Inc. (E), Roche (I); Tushar Bhangale, Genentech, Inc. (E), Roche (I); Phillip Lai, Genentech, Inc. (E), Roche (I); Carole Ho, Genentech, Inc. (E), Roche (I); Eric Strauss, Genentech, Inc. (E), Roche (I)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2234. doi:
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    • Get Citation

      Brian Yaspan, Zhengrong Li, Amy Dressen, Menno van Lookeren Campagne, Robert R Graham, Kha Le, Tushar Bhangale, Phillip Lai, Carole Ho, Eric C Strauss, ; A Common SNP at the CFI Locus is Associated with Rapid Progression of Geographic Atrophy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2234.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

Geographic atrophy (GA) is a progressive advanced form of age-related macular degeneration (AMD). Single nucleotide polymorphisms (SNPs) in genes coding for alternative complement pathway (ACP) proteins are strongly associated with risk for onset of both GA and neovascular subtypes of AMD. The association of these SNPs to the progression of GA area is not well understood. The MAHALO Phase 2 study data were analyzed to evaluate the relationship between published common risk SNPs in the ACP and the progression of GA area.

 
Methods
 

The MAHALO Phase 2 study (NCT01229215) collected whole blood samples for genotyping (Illumina 2.5M Omni SNP array) on 94 patients. From the 94 patients with DNA, 29 received sham injections and completed the study. The relationship between carriers vs. non-carriers of risk SNPs for complement factor H (CFH), complement factor I (CFI), C3, and one SNP tagging both C2 and complement factor B (C2/CFB) was investigated. Tag SNPs for each locus were selected according to a recent genetic meta-analysis containing >17,000 cases and >60,000 controls, and the progression of GA area was evaluated for patients with sham injections.

 
Results
 

Due to small sample size, heterozygotes and homozygotes for the risk alleles were pooled for analysis (n=29). Of the 29 patients, 27, 28, 15 and 12 were risk allele carriers for CFH, C2/CFB, C3 and CFI, respectively. The CFH and C2/CFB SNPs were not informative for analysis due to the high prevalence in the study population. The C3 risk allele did not show a difference in progression of GA between carriers of the C3 risk allele vs. non-carriers of the C3 allele. The CFI risk allele carriers had a change from baseline in GA area at month 18 of 4.169 mm2 compared with 2.792 mm2 in the non-carriers of the CFI risk allele. This corresponds to a 49% increase in GA area growth over 18 months in CFI risk allele carriers compared with non-carriers of the CFI risk allele.

 
Conclusions
 

In the MAHALO study, patients who were carriers of the risk allele for CFI were found to have a faster progression of GA area compared with non-carriers of the CFI risk allele. These results suggest that this common genome-wide association study (GWAS)-associated CFI SNP is prognostic for rapid GA progression. Further studies are needed to confirm the association of CFI with GA progression as well as to elucidate the function of the risk haplotype.

 
Keywords: 412 age-related macular degeneration • 466 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • 539 genetics  
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