Genetic variation in complement regulators and susceptibility to age-related macular degeneration

Immunobiology. 2012 Feb;217(2):158-61. doi: 10.1016/j.imbio.2011.09.002. Epub 2011 Oct 5.

Abstract

Objectives: Age-related macular degeneration (AMD) is the commonest cause of blindness in Western populations. Risk is influenced by age, genetic and environmental factors. Complement activation appears to be important in the pathogenesis and associations have been found between AMD and genetic variations in complement regulators such as complement factor H. We therefore investigated other complement regulators for association with AMD.

Methods: We carried out a case-control study to test for association between AMD and single nucleotide polymorphisms (SNPs) spanning the genes encoding complement factor P (CFP, properdin), CD46 (membrane cofactor protein, MCP), CD55 (decay accelerating factor, DAF) and CD59 (protectin). All cases and controls were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status.

Results: 20 SNPs were genotyped in 446 cases and 262 controls. For two SNPs with p-values approaching significance additional subjects were genotyped to increase the numbers to 622 cases and 359 controls. There was no evidence of association between AMD and any of the SNPs typed in CFP, CD46, CD55 or CD59.

Conclusions: In a case-control sample that has shown the well established associations between AMD and variants in CFH, CFB and C3 there was absence of association with SNPs in CFP, CD46, CD55 and CD59. This suggests that these are not important susceptibility genes for AMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging
  • CD55 Antigens / genetics
  • CD59 Antigens / genetics
  • Case-Control Studies
  • Complement System Proteins / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Genotype
  • Humans
  • Macular Degeneration / genetics*
  • Macular Degeneration / pathology
  • Male
  • Membrane Cofactor Protein / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Properdin / genetics

Substances

  • CD55 Antigens
  • CD59 Antigens
  • Membrane Cofactor Protein
  • Properdin
  • Complement System Proteins