CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration
CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration
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DOI：
10.1159/000094141
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发表时间：
2006-01-01
期刊：
影响因子：
1.8
通讯作者：
Klein, Michael L.
中科院分区：
文献类型：
--
作者：
Seddon, Johanna M.;George, Sarah;Klein, Michael L.
目的：我们检验了这样一个假设，即可改变的生活方式因素改变了与补体因子H（CFH）基因Y 402 H中的常见编码变体相关的遗传易感性，该基因是老年人失明的主要原因，即年龄相关性黄斑变性（AMD）。研究方法：在该病例对照关联分析中，对患有晚期AMD（n = 574例）或无AMD（n = 280例对照）的多中心AMD相关眼病研究中的白人参与者进行了评价。通过眼底照片分级确定AMD状态。评估了包括吸烟和体重指数（BMI）在内的风险因素，并对CFH基因变异体的DNA标本进行了基因分型。进行非条件logistic回归分析。计算归因风险和多变量AMD风险评分。结果：Y 402 H危险等位基因的数量与晚期AMD相关，在控制了人口统计学和行为危险因素后，CT杂合基因型和纯合CC危险基因型的比值比（OR）分别为2.7（95%可信区间（CI）1.8-3.8）和7.4（4.7-11.8）。目前吸烟（OR 5.1）和高BMI >= 30（OR 2.1）与AMD独立相关，控制基因型。AMD和BMI之间的相关性因基因型而异（CT与TT基因型的P交互作用= 0.006）。CC基因型加上更高的BMI（OR 5.9）或吸烟（OR 10.2）带来了最大的风险。基因加环境风险评分提供了0.70-0.75的受试者工作特征（ROC）曲线下面积。结论：遗传和环境因素与晚期AMD独立相关，可改变的因素改变遗传易感性。AMD风险评分可识别高度易感人群。版权所有（c）2006 S. Karger AG，巴塞尔。
Objectives: We tested the hypothesis that modifiable lifestyle factors alter the genetic susceptibility associated with a common coding variant in the complement factor H (CFH) gene, Y402H, for the leading cause of blindness among the elderly, age-related macular degeneration (AMD). Methods: In this case-control association analysis, Caucasian participants in the multicenter Age-Related Eye Disease Study with advanced AMD (n = 574 cases) or no AMD (n = 280 controls) were evaluated. AMD status was determined by grading of fundus photographs. Risk factors including cigarette smoking and body mass index (BMI) were assessed and DNA specimens were genotyped for the variant in the CFH gene. Unconditional logistic regression analyses were performed. Attributable risks and multivariable AMD risk scores were calculated. Results:The number of risk alleles for Y402H was associated with advanced AMD, with odds ratios (OR) of 2.7 (95% confidence interval (CI) 1.8-3.8) for the CT heterozygous genotype and OR 7.4 (4.7-11.8) for the homozygous CC risk genotype, after controlling for demographic and behavioral risk factors. Current cigarette smoking (OR 5.1) and high BMI >= 30 (OR 2.1) were independently related to AMD, controlling for genotype. The association between AMD and BMI varied dependent on genotype (P interaction = 0.006 for the CT vs. TT genotype). The CC genotype plus higher BMI (OR 5.9) or smoking (OR 10.2) conferred the greatest risks. Gene plus environment risk scores provided an area under the receiver operating characteristic (ROC) curve of 0.70-0.75. Conclusions: Genetic and environmental factors are independently related to advanced AMD, and modifiable factors alter genetic susceptibility. The AMD risk score identifies a highly susceptible population. Copyright (c) 2006 S. Karger AG, Basel.