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Association of HLA class I and class II polymorphisms with age-related macular degeneration

Association of HLA class I and class II polymorphisms with age-related macular degeneration
Association of HLA class I and class II polymorphisms with age-related macular degeneration
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.
fluorescent antibody technique, middle aged, immunohistochemistry, polymorphism, research support, methods, extramural, aged, alleles, cohort, p.h.s., linkage disequilibrium, hla antigens, genetics, polymerase chain reaction, elderly, genotype, histocompatibility antigens class i, non-u.s.gov't, human, antigens, histocompatibility antigens class ii, analysis, humans, macular degeneration, male, n.i.h., 80 and over, u.s.gov't, female, indirect, genetic, risk factors
0146-0404
1726-1734
Goverdhan, Srini V.
9ae32d5a-5c82-48a4-962d-1ed8acc3991e
Howell, Martin W.
3e414f47-61a9-4a2d-a1b4-2000b7fc94af
Mullins, Robert F.
794dfee6-5aa1-4e37-93c4-ae5cbce8faf2
Osmond, Clive
2677bf85-494f-4a78-adf8-580e1b8acb81
Hodgkins, Peter R.
28cc9ac1-dcc3-4f60-8858-9b45b6a5cc10
Self, James
0f6efc58-ae24-4667-b8d6-6fafa849e389
Avery, Kim
edd5a988-af0d-4f33-be54-7a015deaf888
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Goverdhan, Srini V.
9ae32d5a-5c82-48a4-962d-1ed8acc3991e
Howell, Martin W.
3e414f47-61a9-4a2d-a1b4-2000b7fc94af
Mullins, Robert F.
794dfee6-5aa1-4e37-93c4-ae5cbce8faf2
Osmond, Clive
2677bf85-494f-4a78-adf8-580e1b8acb81
Hodgkins, Peter R.
28cc9ac1-dcc3-4f60-8858-9b45b6a5cc10
Self, James
0f6efc58-ae24-4667-b8d6-6fafa849e389
Avery, Kim
edd5a988-af0d-4f33-be54-7a015deaf888
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514

Goverdhan, Srini V., Howell, Martin W., Mullins, Robert F., Osmond, Clive, Hodgkins, Peter R., Self, James, Avery, Kim and Lotery, Andrew J. (2005) Association of HLA class I and class II polymorphisms with age-related macular degeneration. Investigative Ophthalmology & Visual Science, 46 (5), 1726-1734. (doi:10.1167/iovs.04-0928). (PMID:15851575)

Record type: Article

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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More information

Published date: May 2005
Keywords: fluorescent antibody technique, middle aged, immunohistochemistry, polymorphism, research support, methods, extramural, aged, alleles, cohort, p.h.s., linkage disequilibrium, hla antigens, genetics, polymerase chain reaction, elderly, genotype, histocompatibility antigens class i, non-u.s.gov't, human, antigens, histocompatibility antigens class ii, analysis, humans, macular degeneration, male, n.i.h., 80 and over, u.s.gov't, female, indirect, genetic, risk factors
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 59776
URI: http://eprints.soton.ac.uk/id/eprint/59776
ISSN: 0146-0404
PURE UUID: 90e97fc5-d427-4e6b-892d-2c9141d7a212
ORCID for Clive Osmond: ORCID iD orcid.org/0000-0002-9054-4655
ORCID for James Self: ORCID iD orcid.org/0000-0002-1030-9963
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 02 Sep 2008
Last modified: 18 Feb 2021 17:06

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Contributors

Author: Srini V. Goverdhan
Author: Martin W. Howell
Author: Robert F. Mullins
Author: Clive Osmond ORCID iD
Author: Peter R. Hodgkins
Author: James Self ORCID iD
Author: Kim Avery

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