HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration
Open accessAbstract
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 understand 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.
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rs11200638 in the HtrA1 promoter is the most well-documented, statistically significant AMD-associated SNP, with odds ratios of 1.60-2.61 in heterozygous and 6.56-10.0 in homozygous individuals (Caucasians, Chinese, Japanese).
“Several studies have shown that rs11200638 in the promoter region is the most well-documented, statistically significant AMD-associated SNP with a high OR of 1.60–2.61 and 6.56–10.0 in heterozygous and homozygous individuals (Caucasians, Chinese and Japanese), respectively (Cameron et al., 2007; Deangelis et al., 2008; Dewan et al., 2006; Mori et al., 2007; Tam et al., 2008; Yang et al., 2006).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Cameron et al., 2007
Elevated expression of HtrA1 mRNA and/or protein in drusen and CNV components has been reported in AMD patients carrying the AA risk genotype.
“Elevated expression of HtrA1 mRNA and/or protein in the drusen and CNV components in AMD patients carrying the AA risk genotype has been reported in several studies (Cameron et al., 2007; Chan et al., 2007; Tuo et al., 2008; Yang et al., 2006) (Fig. 6).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Cameron et al., 2007
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- Authors
- Cameron, D. J., Yang, Z., Gibbs, D., Chen, H., Kaminoh, Y., Jorgensen, A., Zeng, J., Luo, L., Brinton, E., Brinton, G., Brand, J. M., Bernstein, P. S., Zabriskie, N. A., Tang, S., Constantine, R., Tong, Z., & Zhang, K.
- Affiliations
- University of Utah (US)
- Zhongshan Ophthalmic Center, Sun Yat-sen University (CN)
- ORCID
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2007-05-02
- Volume
- 6
- Issue
- 9
- Pages
- 1122-1125
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2154106629
- Cited by
- 114
- References
- 22
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 10 · 2012: 13
- FWCI
- 16.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ronald McDonald House Charities
- Research to Prevent Blindness (P30 EY014800)
- Deutsches Krebsforschungszentrum
- National Institutes of Health (M01-RR00064)
- National Eye Institute (R01EY014448, R01EY014428, R01EY14428, R01EY14448, P30EY014800)
- National Center for Research Resources (M01-RR 00064, M01RR000064)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- HTRA1, geographic atrophy, neovascular age-related macular degeneration, LOC387715, genetic susceptibility, promoter polymorphism, AMD pathogenesis, Utah population
- MeSH terms
- High-Temperature Requirement A Serine Peptidase 1, Gene Frequency, Genotype, Humans, Immunohistochemistry, Macular Degeneration, Risk Factors, Serine Endopeptidases, Genetic Variation, Cohort Studies, Genetic Predisposition to Disease, Choroidal Neovascularization, Polymorphism, Single Nucleotide
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