June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Complement factor B (CFB) polymorphisms and early and late age-related macular degeneration in the EUREYE Study
Author Affiliations & Notes
  • Astrid Fletcher
    Epidemiology & Population Health, London School of Hygiene & Tropical Med, London, United Kingdom
  • Reecha Sofat
    Centre for Clinical Pharmacology, University College, London, United Kingdom
  • Usha Chakravarthy
    Vision Sciences, Queens University, Belfast, United Kingdom
  • Paulus de Jong
    Ophthalmogenetics, Netherlands Institute of Neuroscience, Amsterdam, Netherlands
  • Mati Rahu
    Epidemiology and Biostatistics, National Institute for Health Development, Tallinn, Estonia
  • Jesus Vioque
    Dpto. Salud Publica, Universidad Miguel Hernandez, Alicante, Spain
  • Johan Seland
    Stavanger University Hospital, University of Bergen, Bergen, Norway
  • Fotis Topouzis
    Ophthalmology, Aristotle Univ of Thessaloniki, Thessaloniki, Greece
  • Gisele Soubrane
    Ophthalmology, Univ Paris Descartes, Paris, France
  • Footnotes
    Commercial Relationships Astrid Fletcher, None; Reecha Sofat, None; Usha Chakravarthy, Bayer (C), Novartis (F), Neovista (C), Oraya (F); Paulus de Jong, None; Mati Rahu, None; Jesus Vioque, None; Johan Seland, None; Fotis Topouzis, None; Gisele Soubrane, Allergan (C), Novartis (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 229. doi:
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      Astrid Fletcher, Reecha Sofat, Usha Chakravarthy, Paulus de Jong, Mati Rahu, Jesus Vioque, Johan Seland, Fotis Topouzis, Gisele Soubrane, ; Complement factor B (CFB) polymorphisms and early and late age-related macular degeneration in the EUREYE Study. Invest. Ophthalmol. Vis. Sci. 2013;54(15):229.

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

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Abstract

Purpose: A recent meta-analysis (Thakkinstian Am J Epid 2012; 176:361-372) showed a protective effect of variants in CFB/ Complement component 2 on age-related macular degeneration (AMD). Most studies were of late AMD in clinic patients. Little is known on whether these findings apply to early AMD or whether environmental factors modify the association. We investigated the associations of a variant in CFB (rs4151667) with both early and late AMD in the population based EUREYE study.

Methods: EUREYE was conducted in seven European countries with ethics approval obtained at each centre. Participants gave written informed consent, were interviewed for risk factors and underwent fundus photography and blood collection. Fundus images were graded by an independent reading centre according to the modified International Classification and Grading System for AMD based on staging morphological signs of increasing severity into early AMD (stages 1-3) and late AMD (stage 4). Individuals were genotyped for rs4151667 using KASPar technology. We assessed the effect of genotype (homozygote or heterozygote vs. non risk homozygote) on risk of early and late AMD using multiple logistic regression. Crude and adjusted (age, sex, country) Odds Ratios (ORs) with 95% CI’s were generated. We explored interactions with smoking, obesity, diabetes and cardiovascular disease.

Results: Genotype data were available on 92% of participants (2073 with no AMD (control), 2158 early AMD and 144 late AMD). The rs4151667 control MAF was 0.05 and in Hardy Weinberg equilibrium (p=0.8). Analysis was restricted to the AT vs. TT comparison, as there were only 5 individuals with an AA genotype. The OR and 95% CI were 0.74 (0.58, 0.95) for early AMD and 0.34 (0.14, 0.81) for late AMD. There were significant interactions between smoking and early (p <0.0001) and late (p<0.0001) AMD. In early AMD the OR of AT in never smokers was 0.51 (0.38, 0.68) and in ever smokers, 1.14 (0.81, 1.58). For late AMD the OR was 0.19 (0.05, 0.74) in never smokers and 0.54 (0.26, 1.14) in ever smokers. There were no interactions with the other environmental variables.

Conclusions: We found that rs4151667 was associated with a protective association of early AMD although the effect was smaller compared to late AMD. We report novel results for effect modification by smoking with the lowest ORs reported for non smokers carrying the A allele.

Keywords: 412 age-related macular degeneration • 539 genetics  
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