Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.
PLoS One. 2012;7(2):e31243. doi: 10.1371/journal.pone.0031243. Epub 2012 Feb 15.
Studies that analyzed single nucleotide polymorphisms (SNP) in various genes have shown that genetic factors are strongly associated with age-related macular degeneration (AMD) susceptibility. Copy number variation (CNV) may be an additional type of genetic variation that contributes to AMD pathogenesis. This study investigated CNV in 4 AMD-relevant genes in Korean AMD patients and control subjects.
Four CNV candidate regions located in AMD-relevant genes (VEGFA, ARMS2/HTRA1, CFH and VLDLR), were selected based on the outcomes of our previous study which elucidated common CNVs in the Asian populations. Real-time PCR based TaqMan Copy Number Assays were performed on CNV candidates in 273 AMD patients and 257 control subjects.
The predicted copy number (PCN, 0, 1, 2 or 3+) of each region was called using the CopyCaller program. All candidate genes except ARMS2/HTRA1 showed CNV in at least one individual, in which losses of VEGFA and VLDLR represent novel findings in the Asian population. When the frequencies of PCN were compared, only the gain in VLDLR showed significant differences between AMD patients and control subjects (p = 0.025). Comparisons of the raw copy values (RCV) revealed that 3 of 4 candidate genes showed significant differences (2.03 vs. 1.92 for VEGFA, p<0.01; 2.01 vs. 1.97 for CFH, p<0.01; 1.97 vs. 2.01, p<0.01 for ARMS2/HTRA1).
CNVs located in AMD-relevant genes may be associated with AMD susceptibility. Further investigations encompassing larger patient cohorts are needed to elucidate the role of CNV in AMD pathogenesis.
分析各种基因中单核苷酸多态性（SNP）的研究表明，遗传因素与年龄相关性黄斑变性（AMD）易感性密切相关。拷贝数变异（CNV）可能是导致 AMD 发病机制的另一种遗传变异类型。本研究在韩国 AMD 患者和对照者中检测了 4 个与 AMD 相关的基因中的 CNV。
根据我们之前阐明亚洲人群常见 CNV 的研究结果，选择了位于 AMD 相关基因（VEGFA、ARMS2/HTRA1、CFH 和 VLDLR）中的 4 个 CNV 候选区域。在 273 名 AMD 患者和 257 名对照者中，使用基于实时 PCR 的 TaqMan Copy Number Assays 对 CNV 候选区域进行了检测。
使用 CopyCaller 程序对每个区域的预测拷贝数（PCN，0、1、2 或 3+）进行了调用。除了 ARMS2/HTRA1 之外，所有候选基因在至少一个个体中均存在 CNV，其中 VEGFA 和 VLDLR 的缺失是亚洲人群中的新发现。当比较 PCN 的频率时，只有 VLDLR 的增益在 AMD 患者和对照组之间存在显著差异（p=0.025）。比较原始拷贝值（RCV）发现，4 个候选基因中有 3 个存在显著差异（VEGFA 为 2.03 对 1.92，p<0.01；CFH 为 2.01 对 1.97，p<0.01；ARMS2/HTRA1 为 1.97 对 2.01，p<0.01）。
位于 AMD 相关基因中的 CNV 可能与 AMD 的易感性有关。需要进一步进行包含更大患者队列的研究，以阐明 CNV 在 AMD 发病机制中的作用。
