Ethnic variation in AMD-associated complement factor H polymorphism p.Tyr402His

Hum Mutat. 2006 Sep;27(9):921-5. doi: 10.1002/humu.20359.


Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in the developed world. Previous studies have demonstrated that the c.1204T>C, p.Tyr402His allelic variant in the complement factor H (CFH) gene is associated with an approximately three-fold increased risk for AMD in Caucasians of predominantly European descent. Both the prevalence as well as the phenotypic spectrum of AMD varies widely among persons of different ethnicities. We hypothesized that populations with a lower prevalence of AMD might also have a lower prevalence of the CFH risk allele. In this study we sought to determine the frequency of this sequence variant in control populations of Caucasians, African Americans, Hispanics, Somalis, and Japanese. Normal control populations were assembled for each ethnic group: Caucasian (n=148), Somali (n=128), African American (n=75), Hispanic (n=81), and Japanese (n=82). Individuals were genotyped using a restriction digest assay and the frequency of the C allele at nucleotide position 1204 of the CFH gene was determined. A bioinformatic approach was used to identify SNPs in linkage disequilibrium with rs1061170 (c.1204T>C, p.Tyr402His) from the human haplotype map project database (HapMap) in order to validate the findings. We found widely discordant frequencies of the risk allele between some of the different ethnic groups: Japanese 0.07+/-0.02, Hispanics 0.17+/-0.03, African-Americans 0.35+/-0.04, Caucasians 0.34+/-0.03, and Somalis 0.34+/-0.03. Allele frequencies generated by analysis of the HapMap database were consistent with these findings. This study suggests that there are other yet unidentified genetic factors important in the pathogenesis of AMD that may mitigate the effects of c.1204T>C, p.Tyr402His variant.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Amino Acid Substitution*
  • Complement Factor H / genetics
  • Computational Biology
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haplotypes
  • Histidine / genetics
  • Humans
  • Linkage Disequilibrium
  • Macular Degeneration / diagnosis
  • Macular Degeneration / ethnology*
  • Macular Degeneration / genetics*
  • Middle Aged
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Racial Groups / genetics
  • Risk Factors
  • Tyrosine / genetics
  • White People / genetics


  • CFH protein, human
  • Tyrosine
  • Histidine
  • Complement Factor H