Complement Factor H Polymorphism and Age-Related Macular Degeneration

Science. 2005 Apr 15;308(5720):421-4. doi: 10.1126/science.1110189. Epub 2005 Mar 10.

Abstract

Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association (P = 4.95 x 10(-10)) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 --> histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alleles
  • Amino Acid Substitution
  • Case-Control Studies
  • Chromosomes, Human, Pair 1 / genetics
  • Complement Activation / genetics
  • Complement Factor H / genetics*
  • Complement Factor H / physiology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Haplotypes
  • Histidine
  • Homozygote
  • Humans
  • Linkage Disequilibrium
  • Macular Degeneration / etiology
  • Macular Degeneration / genetics*
  • Male
  • Middle Aged
  • Multigene Family
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Tyrosine

Substances

  • complement factor H, human
  • Tyrosine
  • Histidine
  • Complement Factor H