Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations
Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations
复制标题
鉴定 ANGPT2 作为中国和日本人群中新生血管性年龄相关性黄斑变性和息肉样脉络膜血管病的新基因
DOI：
10.1167/iovs.16-20575
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发表时间：
2017-02-01
影响因子：
4.4
通讯作者：
Chen, Li Jia
中科院分区：
文献类型：
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作者：
Ma, Li;Brelen, Marten E.;Chen, Li Jia
目的。我们确定血管生成素2 （ANGPT2）基因是新生血管性年龄相关性黄斑变性（nAMD）和息肉样脉络膜血管病变（PCV）的一个新的易感基因。在香港华人探索性队列中首次对34个单倍型标记单核苷酸多态性（snp）进行了基因分型。暗示性snp在汕头华人和大阪日本人共2343名受试者中得到重复。对所有受试者的补体因子H （CFH）基因rs800292 SNP进行基因分型。分析遗传关联和基因-基因互作。在香港队列中，ANGPT2中的4个snp （rs13255574、rs4455855、rs13269021和rs11775442）名义上与nAMD和PCV相关。4个ANGPT2 snp在汕头和大阪人群中表现出相同的关联趋势。结合3个研究队列的数据显示，snp rs4455855和rs13269021达到了研究意义（P < 0.0016），使nAMD和PCV的风险增加了约1.3倍。相互作用分析显示，CFH SNP rs800292与ANGPT2 SNP rs13269021在nAMD和PCV中具有高度显著的相互作用。随后的分层分析证实了相互作用。本研究揭示了ANGPT2作为nAMD和PCV新的易感基因，可能与CFH相关影响疾病易感性。因此，本报告为nAMD和PCV的遗传结构提供了新的见解。
PURPOSE. We determine the angiopoietin 2 (ANGPT2) gene as a new susceptibility gene for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).METHODS. A total of 34 haplotype-tagging single-nucleotide polymorphisms (SNPs) were first genotyped in an exploratory Hong Kong Chinese cohort. Suggestive SNPs were replicated in a Shantou Chinese cohort and an Osaka Japanese cohort, with a total of 2343 subjects. The SNP rs800292 in the complement factor H (CFH) gene was genotyped in all the subjects. Genetic association and gene-gene interaction were analyzed.RESULTS. In the Hong Kong cohort, four SNPs in ANGPT2 (rs13255574, rs4455855, rs13269021, and rs11775442) were nominally associated with nAMD and PCV. The four ANGPT2 SNPs showed the same trends of association in the Shantou and Osaka cohorts. Combining the data from the 3 study cohorts revealed that SNPs rs4455855 and rs13269021 achieved study-wise significance (P < 0.0016), conferring an approximately 1.3-fold of increased risk for nAMD and PCV. Interaction analysis revealed the CFH SNP rs800292 has a highly significant interaction with the ANGPT2 SNP rs13269021 in nAMD and PCV in the combined analysis. Subsequent stratification analysis confirmed the interaction.CONCLUSIONS. This study reveals ANGPT2 as a new susceptibility gene for nAMD and PCV, and it may affect disease susceptibility in association with CFH. Thus, this report provides new insights into the genetic architecture of nAMD and PCV.