State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
J Gene Med. 2018 Feb;20(2-3):e3007. doi: 10.1002/jgm.3007. Epub 2018 Feb 12.
Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) share a similar phenotype but are different in their clinical manifestations, responses to treatment and prognosis. Whether PCV is a subtype of AMD or a distinct entity from nAMD remains unknown. Therefore, we performed a whole-exome sequencing based association analysis to compare the genetic architecture of PCV and nAMD in Han Chinese.
Whole-exome sequencing analysis was performed on 21 nAMD cases, 20 PCV cases and 20 healthy controls. As a follow-up validation, 145 nAMD cases, 160 PCV cases and 193 controls were genotyped using the Sequenom MassARRAY platform (Sequenom, San Diego, CA, USA).
A novel variant, c.6196A>G in the IGFN1 gene, was significantly associated with only PCV (combined p = 7.1 × 10 , odds ratio = 9.44), but not with nAMD (combined p = 0.683, odds ratio = 1.30). The minor allele G conferred an increased risk of PCV.
The findings of the present study indicate that, although some of the susceptibility loci are shared between PCV and nAMD, a unique genetic signature may decide the pathogenesis of PCV.
息肉样脉络膜血管病变（PCV）和新生血管性年龄相关性黄斑变性（nAMD）具有相似的表型，但在临床表现、治疗反应和预后方面有所不同。PCV 是否为 AMD 的亚型，或者是否与 nAMD 不同，目前尚不清楚。因此，我们进行了一项基于全外显子组测序的关联分析，以比较汉族人群中 PCV 和 nAMD 的遗传结构。
对 21 例 nAMD 病例、20 例 PCV 病例和 20 例健康对照进行全外显子组测序分析。作为后续验证，使用Sequenom MassARRAY 平台（Sequenom，圣地亚哥，CA，USA）对 145 例 nAMD 病例、160 例 PCV 病例和 193 例对照进行基因分型。
IGFN1 基因中的 c.6196A>G 新变异与仅 PCV 显著相关（合并 p = 7.1×10 ，优势比= 9.44），但与 nAMD 无关（合并 p = 0.683，优势比= 1.30）。次要等位基因 G 增加了 PCV 的发病风险。
本研究的结果表明，尽管 PCV 和 nAMD 之间存在一些易感基因座，但独特的遗传特征可能决定了 PCV 的发病机制。
