Analysis of major alleles associated with age-related macular degeneration in patients with multifocal choroiditis: strong association with complement factor H

Arch Ophthalmol. 2008 Nov;126(11):1562-6. doi: 10.1001/archopht.126.11.1562.

Abstract

Objective: To analyze the frequency of major age-related macular degeneration (AMD)-associated alleles in patients with multifocal choroiditis (MFC).

Methods: A cohort of 48 patients with MFC was compared with previously characterized cohorts of patients with advanced AMD (368 samples) and matched unaffected controls (368 samples). Allele and genotype frequencies of single nucleotide polymorphisms for the following AMD-associated alleles were evaluated: risk alleles in complement factor H (CFH) gene (Y402H and IVS14) and LOC387715/HTRA1 gene on 10q26 (A69S) and protective alleles in CFH (IVS1, IVS6, and delCFHR1-3) and complement factor B loci (H9L and R32Q).

Results: Frequencies of all major AMD-associated alleles in the CFH locus indicate a strong, statistically significant association of CFH gene single nucleotide polymorphisms and MFC. However, the same analysis for the single nucleotide polymorphisms in complement factor B and 10q26 loci matched the results in the control group.

Conclusions: Like AMD, the MFC phenotype is strongly associated with the major alleles/haplotypes in the CFH locus. Clinical Relevance We report compelling evidence of a strong association between CFH polymorphisms and MFC, which contributes to the understanding of MFC pathogenesis and suggests new potential therapeutic targets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles*
  • Choroiditis / genetics*
  • Complement Factor B / genetics
  • Complement Factor H / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Macular Degeneration / genetics*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Proteins / genetics

Substances

  • ARMS2 protein, human
  • CFH protein, human
  • Proteins
  • Complement Factor H
  • Complement Factor B