The HtrA1 promoter polymorphism, smoking, and age-related macular degeneration in multiple case-control samples
Open accessAbstract
Objective To assess the association and combined effect on the risk of age-related macular degeneration (AMD) by the HtrA1 and complement factor H (CFH) polymorphisms, smoking, and serum cholesterol.Design Clinic-based and population-based case control study.Participants A total of 805 AMD cases and 921 controls from The Eye Clinic of National Eye Institute, Age-Related Eye Diseases Study, Blue Mountain Eye Study Cohort, and Minnesota Lions Eye Bank.Methods DNA samples were genotyped for polymorphisms of rs11200638 in HtrA1 promoter and rs380390 in CFH. HtrA1 protein in ocular tissue was measured. Interactions of the HtrA1 risk allele with the CFH risk variant, smoking status, and cholesterol were assessed.Main outcome measures AMD was evaluated by retinal specialists, and AMD subtypes (geographic atrophy and neovascularization) were determined.Results Strong associations of the HtrA1 risk allele (A) with AMD were present in all sample sets. A similar magnitude of association was observed for central geographic atrophy and neovascular AMD. The combination of the HtrA1 and CFH risk alleles increased AMD susceptibility, as did the combination of the HtrA1 risk allele with smoking. No combined effect of HtrA1 risk allele and cholesterol level was found. Enhanced expression of HtrA1 protein was detected in retina with AMD.Conclusions Findings from multiple samples support an AMD genetic variant harbored within HtrA1. The risk of advanced AMD increased when the presence of risk alleles from HtrA1 was combined with either CFH risk alleles or history of smoking.
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rs11200638 is associated with dry AMD with an odds ratio of 2.17 and wet AMD with an odds ratio of 2.97.
“By examining four cohort studies, we have also confirmed this association with ORs of 2.17 and 2.97 for dry and wet AMD, respectively (Tuo et al., 2008).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Tuo et al., 2008
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 Tuo et al., 2008
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References 71 · Cited by 63
- Authors
- Tuo, J., Ross, R. J., Reed, G. F., Yan, Q., Wang, J. J., Bojanowski, C. M., Chew, E. Y., Feng, X., Olsen, T. W., Ferris, F. L., Mitchell, P., & Chan, C.-C.
- Affiliations
- National Institutes of Health (US)
- The University of Sydney (AU)
- University of Minnesota (US)
- Corresponding author
- Chan, Chi-Chao
- ORCID
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 115
- Issue
- 11
- Pages
- 1891-1898
- ISSN
- 0161-6420 (ISSN-L)
- PMC
- PMC2610681
- OpenAlex
- W2036865813
- Cited by
- 63
- References
- 71
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 6 · 2016: 1 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 8
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 EY999999)
- National Institute on Aging (AG025392, R01AG025392)
- National Eye Institute (Z01EY000418, ZIAEY000489)
- 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
- age-related macular degeneration, HTRA1, promoter polymorphism, complement factor H, smoking, serum cholesterol, genetic susceptibility, gene-gene interaction, geographic atrophy, neovascular AMD
- MeSH terms
- High-Temperature Requirement A Serine Peptidase 1, Aged, Cholesterol, Female, Genotype, Humans, Immunoenzyme Techniques, Macular Degeneration, Male, Middle Aged, Promoter Regions, Genetic, Polymorphism, Restriction Fragment Length, Risk Factors, Serine Endopeptidases, Smoking, Case-Control Studies, Polymerase Chain Reaction, Complement Factor H, Polymorphism, Single Nucleotide
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