دورية
Protective effects of an HTRA1insertion–deletion variant against age-related macular degeneration in the Chinese populations
| العنوان: | Protective effects of an HTRA1insertion–deletion variant against age-related macular degeneration in the Chinese populations |
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| المؤلفون: | Ng, Tsz Kin, Liang, Xiao Ying, Lu, Fang, Liu, David TL, Yam, Gary HF, Ma, Li, Tam, Pancy OS, Chen, Haoyu, Cen, Ling Ping, Chen, Li Jia, Yang, Zhenglin, Pang, Chi Pui |
| المصدر: | Laboratory Investigation; January 2017, Vol. 97 Issue: 1 p43-52, 10p |
| مستخلص: | Age-related macular degeneration (AMD) is a leading cause of visual impairment and irreversible blindness in most developed countries, affecting about 50 million elderly people worldwide. Retinal pigment epithelial (RPE) cell degeneration is the pathophysiological cause of AMD, leading to geographic atrophy and choroidal neovascularization. We and others have previously identified several polymorphisms on chromosome 10q26 (HTRA1rs11200638 as well as LOC387715rs10490924 and c.372_815del443ins54) associated with AMD. In this study, we confirmed the association of our previously identified HTRA1insertion–deletion (indel) variant (c.34delCinsTCCT) in 195 exudative AMD patients and 390 controls from the Hong Kong Chinese cohort with additional 168 patients and 210 controls from the Chengdu Chinese cohort and followed by studying its biological functions in RPE cells. Genetic analysis verified the higher prevalence of c.34delCinsTCCT allele in control subjects (8.0%) than in AMD patients (1.9%; P=7.87 × 10−5, odds ratio=0.229). This protective effect was validated as the haplotype of the c.34delCinsTCCT allele existed independent of the risk haplotype (P=1.17 × 10−5). In vitrostudies showed that recombinant HTRA1 c.34delCinsTCCT variant protein was more localized in the endoplasmic reticulum of RPE cells compared with the wild-type 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. We revealed a protective AMD-associated HTRA1variant in Chinese populations and the biological role of HTRA1 in RPE cell degeneration, indicating its involvement in AMD pathogenesis. |
| قاعدة البيانات: | Supplemental Index |
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Full Text Finder | تدمد: | 00236837 15300307 |
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| DOI: | 10.1038/labinvest.2016.117 |