Complement factor H polymorphism in age-related macular degeneration

Science. 2005 Apr 15;308(5720):385-9. doi: 10.1126/science.1109557. Epub 2005 Mar 10.

Abstract

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10(-7)). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Alleles
  • Amino Acid Substitution
  • Case-Control Studies
  • Choroid / immunology
  • Chromosomes, Human, Pair 1 / genetics
  • Complement Factor H / chemistry
  • Complement Factor H / genetics*
  • Complement Factor H / physiology
  • Complement Membrane Attack Complex / analysis
  • Exons
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Histidine / genetics
  • Humans
  • Immunity, Innate
  • Introns
  • Linkage Disequilibrium
  • Macular Degeneration / genetics*
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Pigment Epithelium of Eye / immunology
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Smoking

Substances

  • Complement Membrane Attack Complex
  • Genetic Markers
  • complement factor H, human
  • Histidine
  • Complement Factor H