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. 2011 Mar;129(3):344-51.
doi: 10.1001/archophthalmol.2011.10.

Assessing susceptibility to age-related macular degeneration with genetic markers and environmental factors

Yuhong Chen  1 , Jiexi Zeng, Chao Zhao, Kevin Wang, Elizabeth Trood, Jeanette Buehler, Matthew Weed, Daniel Kasuga, Paul S Bernstein, Guy Hughes, Victoria Fu, Jessica Chin, Clara Lee, Maureen Crocker, Matthew Bedell, Francesca Salasar, Zhenglin Yang, Michael Goldbaum, Henry Ferreyra, William R Freeman, Igor Kozak, Kang Zhang
Affiliations

Assessing susceptibility to age-related macular degeneration with genetic markers and environmental factors

Yuhong Chen et al. Arch Ophthalmol. 2011 Mar.

Abstract

Objectives: To evaluate the independent and joint effects of genetic factors and environmental variables on advanced forms of age-related macular degeneration (AMD), including geographic atrophy and choroidal neovascularization, and to develop a predictive model with genetic and environmental factors included.

Methods: Demographic information, including age at onset, smoking status, and body mass index, was collected for 1844 participants. Genotypes were evaluated for 8 variants in 5 genes related to AMD. Unconditional logistic regression analyses were performed to generate a risk predictive model.

Results: All genetic variants showed a strong association with AMD. Multivariate odds ratios were 3.52 (95% confidence interval, 2.08-5.94) for complement factor H, CFH rs1061170 CC, 4.21 (2.30-7.70) for CFH rs2274700 CC, 0.46 (0.27-0.80) for C2 rs9332739 CC/CG, 0.44 (0.30-0.66) for CFB rs641153 TT/CT, 10.99 (6.04-19.97) for HTRA1/LOC387715 rs10490924 TT, and 2.66 (1.43-4.96) for C3 rs2230199 GG. Smoking was independently associated with advanced AMD after controlling for age, sex, body mass index, and all genetic variants.

Conclusion: CFH confers more risk to the bilaterality of geographic atrophy, whereas HTRA1/LOC387715 contributes more to the bilaterality of choroidal neovascularization. C3 confers more risk for geographic atrophy than choroidal neovascularization. Risk models with combined genetic and environmental factors have notable discrimination power.

Clinical relevance: Early detection and risk prediction of AMD could help to improve the prognosis of AMD and to reduce the outcome of blindness. Targeting high-risk individuals for surveillance and clinical interventions may help reduce disease burden.

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Figures

Figure 1
Figure 1
Association of age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) in bilaterally affected and unilaterally affected patients. *Indicates P<.05. †Indicates P<.001. Odds ratios of bilateral and unilateral AMD (A), bilateral and unilateral CNV (B), and bilateral and unilateral GA (C) compared with control individuals. Error bars indicate 95% confidence intervals of the odds ratios.
Figure 2
Figure 2
Joint effects of CFH rs2274700, HTRA1/LOC387715 rs10490924, C3 rs2230199, and smoking status were shown with odds ratios calculated by logistic regression model, adjusted for age, sex, body mass index, and other genetic variants. SMK0, SMK1, and SMK2 indicate never smoker, ever smoker, and current smoker, respectively; 700, 924, and 199 indicate CFH rs2274700, HTRA1/LOC387715 rs10490924, and C3 rs2230199, respectively.
Figure 3
Figure 3
Sensitivities and specificities for a variety of risk score cutoffs and receiver operating characteristic (ROC) curve for risk of age-related macular degeneration. Area under the ROC curve=0.82.
See this image and copyright information in PMC

References

    1. Edwards AO, Ritter R, III, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science. 2005;308(5720):421–424. - PubMed
    1. Haines JL, Hauser MA, Schmidt S, et al. Complement factor H variant increases the risk of age-related macular degeneration. Science. 2005;308(5720):419–421. - PubMed
    1. Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308(5720):385–389. - PMC - PubMed
    1. Dewan A, Liu M, Hartman S, et al. HTRA1 promoter polymorphism in wet age-related macular degeneration. Science. 2006;314(5801):989–992. - PubMed
    1. Yang Z, Camp NJ, Sun H, et al. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 2006;314(5801):992–993. - PubMed

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