Copy Number Variations in Candidate Genes in Neovascular Age-Related Macular Degeneration
Copy Number Variations in Candidate Genes in Neovascular Age-Related Macular Degeneration
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DOI：
10.1167/iovs.10-6735
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发表时间：
2011-05-01
影响因子：
4.4
通讯作者：
Tuo, Jingsheng
中科院分区：
文献类型：
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作者：
Liu, Melissa M.;Agron, Elvira;Tuo, Jingsheng
目的.年龄相关性黄斑变性（AMD）的发病机制受到遗传因素的强烈影响，单核苷酸多态性一直与AMD相关。拷贝数变异（CNV）或特定DNA片段拷贝数的变异也可能导致AMD发病机制。本研究评估了已报道与AMD相关的候选基因中的CNVs。研究参与者是131名新生血管性AMD患者和103名无AMD的老年人，他们由国家眼科研究所的视网膜专家进行评估。从外周全血中收集DNA，并对基因CCR 3、CFH、CX 3CR 1、ERCC 6、HTRA 1和VEGF进行基于双重RT-PCR的拷贝数（CN）测定。对氯化萘（氯化萘= 0、1、2或3+）进行了定量测定。在CCR 3、CX 3CR 1和ERCC 6中发现了新的CNV。未校正的数据表明，CN = 3+的CX 3CR 1可能对AMD有轻度保护作用，但在校正年龄后，这种趋势并不持续。AMD患者的平均CFH CN似乎高于对照组（2.13 [95%置信区间（CI），2.05-2.21] vs. 2.01 [95% CI，1.92-2.09拷贝]; P = 0.05）。CNV与AMD的相关性不显著。所描述的方法适用于定量表征候选基因中的CNV。作者鉴定了AMD相关基因中的CNV，但没有发现与新生血管性AMD相关的强有力证据。（Invest Ophthalmol维斯科学。2011;52：3129-3135）DOI：10.1167/iovs.10-6735
PURPOSE. The pathogenesis of age-related macular degeneration (AMD) is strongly influenced by genetic factors, and single nucleotide polymorphisms have been consistently linked to AMD. Copy number variation (CNV), or variation in the number of copies of a particular segment of DNA, may also contribute to AMD pathogenesis. This study evaluated CNVs in candidate genes that have been reported to be linked to AMD.METHODS. Study participants were 131 patients with neovascular AMD and 103 elderly persons without AMD who were evaluated by retinal specialists at the National Eye Institute. DNA was collected from peripheral whole blood, and duplex RT-PCR based copy number (CN) assays were performed for the genes CCR3, CFH, CX3CR1, ERCC6, HTRA1, and VEGF. Quantitative CNs (CN = 0, 1, 2, or 3+) were determined.RESULTS. Novel CNVs were discovered in CCR3, CX3CR1, and ERCC6. The unadjusted data suggested that CN = 3+ for CX3CR1 might be mildly protective against AMD, but this trend did not persist after adjustment for age. AMD patients appeared to have an elevated mean CFH CN relative to controls (2.13 [95% confidence interval (CI), 2.05-2.21] vs. 2.01 [95% CI, 1.92-2.09 copies]; P = 0.05). No significant associations between CNV and AMD were observed for the remaining genes.CONCLUSIONS. The methods described are suitable for quantitative characterization of CNV in candidate genes. The authors identified CNVs in AMD-associated genes but did not find strong evidence for a link with neovascular AMD. (Invest Ophthalmol Vis Sci. 2011;52:3129-3135) DOI:10.1167/iovs.10-6735