CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses
Open accessAbstract
Age-related maculopathy (ARM) is an important cause of visual impairment in the elderly population. It is of crucial importance to identify genetic factors and their interactions with environmental exposures for this disorder. This study was aimed at investigating the CFH, ELOVL4, PLEKHA1 and LOC387715 genes in independent cohorts collected using different ascertainment schemes. The study used a case-control design with subjects originally recruited through the Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS). CFH was significantly associated with ARM in both cohorts (P</=0.00001). A meta-analysis confirmed that the risk allele in the heterozygous or homozygous state (OR, 2.4 and 6.2; 95% CI, 2.2-2.7 and 5.4-7.2, respectively) confers susceptibility. LOC387715 was also significantly associated with ARM in both cohorts (P</=0.00001) and a meta-analysis confirmed that the risk allele in the heterozygous and homozygous state (OR, 2.5 and 7.3; 95% CI, 2.2-2.9 and 5.7-9.4, respectively) confers susceptibility. Both CFH and LOC387715 showed an allele-dose effect on the ARM risk, individuals homozygous at either locus were at more than two-fold risk compared to those heterozygous. PLEKHA1, which is closely linked to LOC387715, was significantly associated with ARM status in the AREDS cohort, but not the CHS cohort and ELOVL4 was not significantly associated with ARM in either cohort. Joint action of CFH and LOC387715 was best described by independent multiplicative effect without significant interaction in both cohorts. Interaction of both genes with cigarette smoking was insignificant in both cohorts. This study provides additional support for the CFH and LOC387715 genes in ARM susceptibility via the evaluation of cohorts that had different ascertainment schemes regarding ARM status and through the meta-analyses.
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The association of the ARMS2 gene with AMD, especially advanced AMD, has been replicated in many independent studies.
“The association of ARMS2 gene with AMD, especially advanced AMD, susceptibility has now been replicated in numbers of independent studies (Conley et al., 2006; Rivera et al., 2005; Ross et al., 2007; Schmidt et al., 2006; Seddon et al., 2007; Kanda et al., 2007).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Conley et al., 2006
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- Authors
- Conley, Y. P., Jakobsdottir, J., Mah, T., Weeks, D. E., Klein, R., Kuller, L., Ferrell, R. E., & Gorin, M. B.
- Affiliations
- University of Pittsburgh (US)
- University of Wisconsin–Madison (US)
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-09-25
- Volume
- 15
- Issue
- 21
- Pages
- 3206-3218
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2110658384
- Cited by
- 157
- References
- 44
- Citations by year
- 2025: 1 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 1 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 8 · 2013: 11 · 2012: 19
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Eye and Ear Foundation of Pittsburgh
- Research to Prevent Blindness
- National Institutes of Health (n01hc085079-024, n01hc015103-009, n01hc085086-022, n01hc55222-0-0-0, n01hc035129-010)
- National Heart, Lung, and Blood Institute (N01HC15103, N01 HC85086, N01 HC55222, U01HL080295, N01-HC85079, N01HC35129)
- National Eye Institute (R01EY009859)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- age-related maculopathy, CFH gene, genetic susceptibility, gene-gene interaction, cigarette smoking, AREDS, Cardiovascular Health Study, macular degeneration
- MeSH terms
- Aged, Aged, 80 and over, Eye Proteins, Female, Humans, Macular Degeneration, Male, Membrane Proteins, Proteins, Cohort Studies, Case-Control Studies, Complement Factor H, Genetic Predisposition to Disease, Intracellular Signaling Peptides and Proteins
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