September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Protective effects of a HTRA1 insertion-deletion variant against age-related macular degeneration
Author Affiliations & Notes
  • Tsz Kin Ng
    Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong
  • Xiao Ying Liang
    Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong
  • David T.L. Liu
    Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong
  • Gary Hin-Fai Yam
    Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong
  • Fang Lu
    Sichuan Academy of Medical Sciences , Chengdu, China
  • Li Ma
    Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong
  • Pancy OS Tam
    Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong
  • Li Jia Chen
    Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong
  • Zhenglin Yang
    Sichuan Academy of Medical Sciences , Chengdu, China
  • Chi Pui Calvin Pang
    Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong
  • Footnotes
    Commercial Relationships   Tsz Kin Ng, None; Xiao Ying Liang, None; David Liu, None; Gary Hin-Fai Yam, None; Fang Lu, None; Li Ma, None; Pancy OS Tam, None; Li Jia Chen, None; Zhenglin Yang, None; Chi Pui Pang, None
  • Footnotes
    Support  This study was supported by a block grant from the University Grants Committee, a Direct Grant from the Medical Panel, the Chinese University of Hong Kong (grant number: 4054119) and the General Research Fund from the Research Grants Council (grant number: 473410), Hong Kong, and National Natural Science Foundation of China (grant number: 81025006).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2633. doi:
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    • Get Citation

      Tsz Kin Ng, Xiao Ying Liang, David T.L. Liu, Gary Hin-Fai Yam, Fang Lu, Li Ma, Pancy OS Tam, Li Jia Chen, Zhenglin Yang, Chi Pui Calvin Pang; Protective effects of a HTRA1 insertion-deletion variant against age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2633.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Common polymorphisms are prone to show stronger association with diseases than rare variants because of higher minor allele frequencies. In contract, rare variants in coding regions could be more related to the functions of the proteins. In this study, we investigated the genetic association and biological functions of our previously identified HTRA1 insertion-deletion (indel) variant (c.34delCinsTCCT).

Methods : Two Chinese exudative AMD cohorts with totally 963 subjects were recruited for the genetic association study. Wildtype HTRA1 and variant were cloned and expressed in retinal pigment epithelial (RPE) cells, followed by the characterization of their biological functions.

Results : Genetic analysis verified the higher prevalence of c.34delCinsTCCT allele in control subjects than in AMD patients (p = 8.33 x 10-5, odds ratio = 0.226). This protective effect was validated as the haplotype of the c.34delCinsTCCT allele existed independent of the risk haplotype (p = 6.23 x 10-5). In vitro studies showed that recombinant HTRA1 c.34delCinsTCCT variant protein was more localized in the endoplasmic reticulum of RPE cells compared to the wildtype protein, and its secretion was delayed. Moreover, ARPE-19 cells expressing HTRA1 c.34delCinsTCCT variant had higher cell viability, lower cell apoptosis and were less responsive to anoikis, supporting its protective role.

Conclusions : Our results revealed a protective HTRA1 variant against HTRA1-induced RPE cell death, indicating its involvement in AMD pathogenesis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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