HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration

被引:93
作者
Cameron, D. Joshua
Yang, Zhenglin
Gibbs, Daniel
Chen, Haoyu
Kaminoh, Yuuki
Jorgensen, Adam
Zeng, Jesse
Luo, Ling
Brinton, Eric
Brinton, Gregory
Brand, John M.
Bernstein, Paul S.
Zabriskie, Norman A.
Tang, Shibo
Constantine, Ryan
Tong, Zongzhong
Zhang, Kang
机构
[1] Univ Utah, Moran Eye Ctr, Sch Med, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA
[2] Sichuan Med Sci Acad, Sichuan, Peoples R China
[3] Sichuan Prov Peoples Hosp, Sichuan, Peoples R China
[4] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou, Peoples R China
[5] Retina Associates Utah, Holladay, UT USA
关键词
age-related macular degeneration; HTRA1; geographic atrophy; drusen; genetics; association;
D O I
10.4161/cc.6.9.4157
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better under stand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.
引用
收藏
页码:1122 / 1125
页数:4
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