Association of HLA Class I and Class II Polymorphisms with Age-Related Macular Degeneration
Abstract
PURPOSE: To evaluate whether HLA genotypes are associated with age-related macular degeneration (AMD). METHODS: HLA class I-A, -B, and -Cw and class II DRB1 and DQB1 principal allele groups were genotyped in two stages: initially for principal allele groups in a cohort of 100 AMD cases and 92 control subjects, and then, in the next 100 cases and controls from the same cohort, for alleles or allele groups with P < 0.1 on initial typing. Genotype frequencies were compared by 2 x 2 contingency tables. The strongest associations for individual HLA alleles were calculated with two-locus stratification analysis and logistic regression for all possible pair-wise HLA combinations. Bonferroni corrections were applied for multiple measurements (P(c)). Each HLA allele was subjected to logistic regression for known AMD covariates. HLA immunohistochemistry for class I antigens was performed on elderly donor eyes. RESULTS: Allele Cw*0701 (P = 0.004, P(c) = 0.036) correlated positively with AMD, whereas alleles B*4001 (P = 0.003, P(c) = 0.027) and DRB1*1301(P = 0.001, P(c) = 0.009) were negatively associated. These HLA associations were independent of any linkage disequilibrium. Immunohistochemistry demonstrated differential HLA class I expression in choriocapillary endothelial cells. CONCLUSIONS: Significant positive and negative associations exist between HLA alleles and AMD. HLA polymorphisms influence the development of AMD, possibly via modulating choroidal immune function.
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Multiple associations between AMD and HLA and cytokine genes have also been reported.
“Multiple associations between AMD and HLA and cytokine genes have also been reported (57, 58).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [58]
Multiple associations between AMD and HLA and cytokine genes have been reported.
“Multiple associations between AMD and HLA and cytokine genes have also been reported (57, 58).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [58]
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- Authors
- Goverdhan, S. V., Howell, M. W., Mullins, R. F., Osmond, C., Hodgkins, P. R., Self, J., Avery, K., & Lotery, A. J.
- Affiliations
- From the Human Genetics Division and the2Southampton Eye Unit, and
- University Hospital Southampton NHS Foundation Trust (GB)
- University of Iowa (US)
- University of Southampton (GB)
- Southampton Eye Unit, and
- From the Human Genetics Division and the
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2005-05-01
- Volume
- 46
- Issue
- 5
- Pages
- 1726
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2032178201
- Cited by
- 78
- References
- 56
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 5
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- Wellcome Trust
- Centers for Disease Control and Prevention
- National Eye Institute (EY-014563, R03EY014563)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- age-related macular degeneration, HLA polymorphism, HLA class I, HLA class II, HLA-DRB1*1301, HLA-DQB1, genetic association
- MeSH terms
- Aged, Aged, 80 and over, Alleles, Histocompatibility Antigens Class II, Female, Genotype, HLA Antigens, Humans, Macular Degeneration, Male, Middle Aged, Polymorphism, Genetic, Risk Factors, Histocompatibility Antigens Class I, Polymerase Chain Reaction, Fluorescent Antibody Technique, Indirect
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