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  • Identification of TIE2 as a susceptibility gene for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

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Laboratory science
Identification of TIE2 as a susceptibility gene for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy
  1. Zhen Ji Chen1,
  2. Li Ma1,2,
  3. Marten E Brelen1,3,
  4. Haoyu Chen4,
  5. Motokazu Tsujikawa5,
  6. Timothy Y Lai1,
  7. Mary Ho3,
  8. Kaori Sayanagi5,
  9. Chikako Hara5,
  10. Noriyasu Hashida5,
  11. Pancy OS Tam1,
  12. Alvin L Young1,3,
  13. Kohji Nishida5,
  14. Clement C Tham1,6,
  15. Chi Pui Pang1,
  16. Li Jia Chen1,3
  1. 1 Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  2. 2 Current affiliation: Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
  3. 3 Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Shatin, Hong Kong
  4. 4 Joint Shantou International Eye Center, Shantou, China
  5. 5 Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
  6. 6 Hong Kong Eye Hospital, Hong Kong, China
  1. Correspondence to Dr Li Jia Chen, Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong; lijia_chen{at}cuhk.edu.hk

Abstract

Purpose The endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of the TIE2 (tyrosine kinase, endothelial, TEK) gene with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using haplotype-tagging single-nucleotide polymorphisms (SNPs) analysis.

Methods This study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs in TIE2 were genotyped in the Hong Kong cohort using TaqMan technology. Two SNPs (rs625767 and rs2273717) showing association in the Hong Kong cohort were genotyped in the Shantou and Osaka cohorts. The SNP-disease association of individual and pooled cohorts were analysed.

Results Two SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; I2=0%), PCV (p=0.02; OR=0.83, 95% CI 0.71 to 0.97; I2=27%) and pooled nAMD and PCV (p=0.002; OR=0.82, 95% CI 0.72 to 0.93; I2=0%), with low inter-cohort heterogeneities.

Conclusion This study revealed TIE2 as a novel susceptibility gene for nAMD and PCV in Japanese and Chinese. Further studies in other populations are warranted to confirm its role.

  • genetics
  • macula
  • experimental–laboratory
  • neovascularisation

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Data are available upon reasonable request.

https://doi.org/10.1136/bjophthalmol-2019-315746

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information. Data are available upon reasonable request.

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    Footnotes

    • ZJC and LM contributed equally.

    • Contributors LJC and CPP conceived the idea and designed the study. MB, HC, MT, TYYL, MH, KS, CH, NH, ALY, KN, CCT and LJC recruited the study subjects and performed clinical examinations. ZJC, LM and POST performed the experiments and collected data. ZJC, LM and LJC analysed the data and wrote the manuscript. LJC, CCT, ALY and CPP revised the paper. All authors approved the submitted version.

    • Funding This study was supported in part by the General Research Fund, Hong Kong (14120516 (LJC)), Direct Grant of Chinese University of Hong Kong Medical Panel, Hong Kong (4054281 (LJC)), National Natural Science Foundation of China (NSFC, 81500764 (LJC)), and the Endowment Fund for Lim Por-Yen Eye Genetics Research Centre, Hong Kong.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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