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Srini V. Goverdhan, Martin W. Howell, Robert F. Mullins, Clive Osmond, Peter R. Hodgkins, James Self, Kim Avery, Andrew J. Lotery; Association of HLA Class I and Class II Polymorphisms with Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2005;46(5):1726-1734. doi: 10.1167/iovs.04-0928.
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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 × 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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