Association of HLA class I and class II polymorphisms with age-related macular degeneration.
OBJECTIVE
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.
Goverdhan
Srini V
SV
Human Genetics Division, University of Southampton, Duthie Building, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
Howell
Martin W
MW
Mullins
Robert F
RF
Osmond
Clive
C
Hodgkins
Peter R
PR
Self
James
J
Avery
Kim
K
Lotery
Andrew J
AJ
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II