Age-Related Macular Degeneration Is Associated with the HLA-Cw*0701 Genotype and the Natural Killer Cell Receptor AA Haplotype
2008
PURPOSE. To determine the association of Human Leucocyte 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 using the PCR-SSP. METHOD. This cohort was then genotyped for 16 KIR genes by PCR-SSP. Frequencies of the tested HLA / KIR alleles were then compared between AMD patients and normal controls. HLA C1, Cw*07, Cw*0701 genotypes and their combinations with KIR genotypes/haplotypes were tested for association with AMD. P values were obtained using a 2-tailed chi-squared test and Bonferroni corrections applied for multiple testing (Pc). RESULTS. The HLA Cw*0701 allele in combination with the inhibitory KIR AA haplotype was associated with AMD following logistic regression analysis (P=0.006, Pc=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 required to confirm these novel HLA-KIR associations with AMD.
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