Chen Yuhong, Zeng Jiexi, Zhao Chao, Wang Kevin, Trood Elizabeth, Buehler Jeanette, Weed Matthew, Kasuga Daniel, Bernstein Paul S, Hughes Guy, Fu Victoria, Chin Jessica, Lee Clara, Crocker Maureen, Bedell Matthew, Salasar Francesca, Yang Zhenglin, Goldbaum Michael, Ferreyra Henry, Freeman William R, Kozak Igor, Zhang Kang
Institute for Genomic Medicine and Shiley Eye Center, University of California, San Diego, USA.
Arch Ophthalmol. 2011 Mar;129(3):344-51. doi: 10.1001/archophthalmol.2011.10.
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.
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.
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.
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.
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.
评估遗传因素和环境变量对年龄相关性黄斑变性（AMD）晚期形式（包括地图状萎缩和脉络膜新生血管形成）的独立及联合作用，并建立一个包含遗传和环境因素的预测模型。
收集了1844名参与者的人口统计学信息，包括发病年龄、吸烟状况和体重指数。对与AMD相关的5个基因中的8个变异进行了基因分型评估。进行无条件逻辑回归分析以生成风险预测模型。
所有基因变异均与AMD有强关联。补体因子H（CFH）rs1061170 CC的多变量优势比为3.52（95%置信区间，2.08 - 5.94），CFH rs2274700 CC为4.21（2.30 - 7.70），C2 rs9332739 CC/CG为0.46（0.27 - 0.80），CFB rs641153 TT/CT为0.44（0.30 - 0.66），HTRA1/LOC387715 rs10490924 TT为10.99（6.04 - 19.97），C3 rs2230199 GG为2.66（1.43 - 4.96）。在控制年龄、性别、体重指数和所有基因变异后，吸烟与晚期AMD独立相关。
CFH对地图状萎缩的双侧性赋予更多风险，而HTRA1/LOC387715对脉络膜新生血管形成的双侧性贡献更大。C3对地图状萎缩的风险赋予比脉络膜新生血管形成更多。包含遗传和环境因素的风险模型具有显著的判别能力。
AMD的早期检测和风险预测有助于改善AMD的预后并降低失明结局。针对高危个体进行监测和临床干预可能有助于减轻疾病负担。
