Age-related macular degeneration is associated with the HLA-Cw*0701 Genotype and the natural killer cell receptor AA haplotype.
OBJECTIVE
To determine the association of human leukocyte antigen (HLA) C and its cognate killer cell immunoglobulin-like receptor (KIR) ligands with age-related macular degeneration (AMD).


METHODS
HLA class I allele groups including the HLA-C principal alleles were genotyped in a cohort of 104 AMD cases and 93 controls by using the PCR-SSP (sequence-specific primers)


METHODS
This cohort was then genotyped for 16 KIR genes by PCR-SSP. Frequencies of the tested HLA/KIR alleles were then compared between patients with AMD and normal control subjects. HLA-C1, -Cw*07, and -Cw*0701 genotypes and their combinations with KIR genotypes/haplotypes were tested for association with AMD. Probabilities were obtained with a two-tailed chi(2) test and Bonferroni correction applied for multiple testing (P(c)).


RESULTS
The HLA-Cw*0701 allele, in combination with the inhibitory KIR AA haplotype was associated with AMD after logistic regression analysis (P = 0.006, P(c) = 0.036, OR = 4.35, 95% CI = 1.41-13.44).


CONCLUSIONS
The HLA-Cw*0701 allele and KIR haplotype AA are associated with AMD. This genotype combination suggests that natural killer cells have a role in the pathogenesis of AMD. Replication studies are needed to confirm these novel HLA-KIR associations with AMD.
Goverdhan
Srinivas V
SV
Division of Clinical Neurosciences, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
Khakoo
Salim I
SI
Gaston
Hannah
H
Chen
Xiaoli
X
Lotery
Andrew J
AJ
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D054340:Receptors, KIR / Q000235:genetics*
D015236:HLA-C Antigens; D054340:Receptors, KIR; D004247:DNA