title: Association of HLA class I and class II polymorphisms with age-related macular degeneration.
abstract: 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.
authors.affiliation: Human Genetics Division, University of Southampton, Duthie Building, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
authors.forename: Srini V
authors.initials: SV
authors.lastname: Goverdhan
authors.forename: Martin W
authors.initials: MW
authors.lastname: Howell
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Clive
authors.initials: C
authors.lastname: Osmond
authors.forename: Peter R
authors.initials: PR
authors.lastname: Hodgkins
authors.forename: James
authors.initials: J
authors.lastname: Self
authors.forename: Kim
authors.initials: K
authors.lastname: Avery
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lotery
mesh_terms: 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
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II