Age-Related Macular Degeneration Is Associated with the HLA-Cw*0701 Genotype and the Natural Killer Cell Receptor AA Haplotype

PURPOSE: 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) METHOD: 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.