May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
HLA Cw*0701 Genotype and Natural Killer Cell Receptor AA Haplotype Are Associated With Age-Related Macular Degeneration
Author Affiliations & Notes
  • S. V. Goverdhan
    University of Southampton, Southampton, United Kingdom
    Clinical Neurosciences Division,
  • S. I. Khakoo
    Division of Medicine, Imperial College of London, London, United Kingdom
  • H. Gaston
    University of Southampton, Southampton, United Kingdom
    Southampton Eye Unit,
  • H. Griffiths
    University of Southampton, Southampton, United Kingdom
    Clinical Neurosciences Division,
  • A. J. Lotery
    University of Southampton, Southampton, United Kingdom
    Clinical Neurosciences Division,
  • Footnotes
    Commercial Relationships  S.V. Goverdhan, None; S.I. Khakoo, None; H. Gaston, None; H. Griffiths, None; A.J. Lotery, None.
  • Footnotes
    Support  American Health Assistance Foundation,NHS Research and Development fellowship, British Council of Prevention of Blindness.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 203. doi:https://doi.org/
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      S. V. Goverdhan, S. I. Khakoo, H. Gaston, H. Griffiths, A. J. Lotery; HLA Cw*0701 Genotype and Natural Killer Cell Receptor AA Haplotype Are Associated With Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):203. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The role of inflammatory events in Age related macular degeneration (AMD) is now well established. HLA genotypes have previously been associated with AMD. HLA class I molecules are ligands for killer-cell immunoglobulin-like receptors (KIRs) which are expressed predominantly by natural killer (NK) cells. NK cells are involved in early responses against infected or transformed cells by production of cytokines and direct cytotoxicity. We hypothesised that certain combinations of HLA Cw and KIR gene variants may influence susceptibility to AMD. To test this we evaluated the association of HLA Cw and it’s cognate KIR (killer-cell immunoglobulin-like receptor) ligands with AMD.

Methods: : HLA C principal allele groups were genotyped in a cohort of 104 AMD cases and 93 controls from Southampton using 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 2-tailed chi-squared test and bonferroni corrections applied for multiple testing (Pc).

Results: : HLA Cw*0701 allele in combination with the inhibitory KIR AA haplotype was seen to strongly associate with AMD status following logistic regression analysis (P=0.006, Pc=0.036, OR= 4.35, 95% CI =1.41-13.44).

Conclusions: : HLA Cw*0701 and KIR haplotypes AA are associated with AMD. This genotype combination could play an important role in AMD. Natural killer cells may therefore have a role in the pathogenesis of AMD.

Keywords: age-related macular degeneration • inflammation • genetics 
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