Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3129-35. doi: 10.1167/iovs.10-6735.
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.
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.
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.
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.
年龄相关性黄斑变性（AMD）的发病机制受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），即特定 DNA 片段的拷贝数的变化，也可能导致 AMD 的发病机制。本研究评估了已报道与 AMD 相关的候选基因中的 CNV。
研究参与者包括 131 名新生血管性 AMD 患者和 103 名经国家眼科研究所视网膜专家评估的无 AMD 老年患者。从外周全血中收集 DNA，并对 CCR3、CFH、CX3CR1、ERCC6、HTRA1 和 VEGF 基因进行基于双 RT-PCR 的拷贝数（CN）检测。确定定量 CN（CN=0、1、2 或 3+）。
在 CCR3、CX3CR1 和 ERCC6 中发现了新的 CNV。未经调整的数据表明，CX3CR1 的 CN=3+可能对 AMD 有轻度保护作用，但在调整年龄后，这种趋势并未持续。AMD 患者的 CFH CN 平均值相对于对照组升高（2.13[95%置信区间（CI），2.05-2.21]与 2.01[95%CI，1.92-2.09 拷贝]；P=0.05）。在其余基因中，未观察到 CNV 与 AMD 之间存在显著关联。
所描述的方法适用于候选基因中 CNV 的定量特征描述。作者在 AMD 相关基因中发现了 CNV，但没有发现与新生血管性 AMD 有很强关联的证据。
