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

Srini V Goverdhan; Martin W Howell; Robert F Mullins; Clive Osmond; Peter R Hodgkins; James Self; Kim Avery; Andrew J Lotery

doi:10.1167/iovs.04-0928

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

Journal article

Peer reviewed

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

Srini V Goverdhan, Martin W Howell, Robert F Mullins, Clive Osmond, Peter R Hodgkins, James Self, Kim Avery and Andrew J Lotery

Investigative ophthalmology & visual science, Vol.46(5), pp.1726-1734

05/2005

DOI: 10.1167/iovs.04-0928

PMID: 15851575

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Abstract

To evaluate whether HLA genotypes are associated with age-related macular degeneration (AMD). 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. 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. Significant positive and negative associations exist between HLA alleles and AMD. HLA polymorphisms influence the development of AMD, possibly via modulating choroidal immune function.

Humans

Middle Aged

Risk Factors

Genotype

Male

Histocompatibility Antigens Class I - genetics

HLA Antigens - genetics

Polymorphism, Genetic

Macular Degeneration - genetics

Alleles

Polymerase Chain Reaction

Aged, 80 and over

Female

Aged

Histocompatibility Antigens Class II - genetics

Fluorescent Antibody Technique, Indirect

Details

Title: Subtitle: Association of HLA class I and class II polymorphisms with age-related macular degeneration
Creators: Srini V Goverdhan - Human Genetics Division, University of Southampton, Duthie Building, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
Martin W Howell
Robert F Mullins
Clive Osmond
Peter R Hodgkins
James Self
Kim Avery
Andrew J Lotery
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.46(5), pp.1726-1734
DOI: 10.1167/iovs.04-0928
PMID: 15851575
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: EY 014563 / NEI NIH HHS
Language: English
Date published: 05/2005
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983980010802771

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