Three major loci involved in age-related macular degeneration are also associated with polypoidal choroidal vasculopathy

Ophthalmology. 2010 Aug;117(8):1567-70. doi: 10.1016/j.ophtha.2009.12.018. Epub 2010 Apr 8.

Abstract

Purpose: To investigate the frequency of variants in 3 major age-related macular degeneration (AMD)-associated loci in patients of European-American descent with polypoidal choroidal vasculopathy (PCV).

Design: Cross-sectional, case-control association study.

Participants: Fifty-five patients with PCV, 368 patients with advanced AMD, and 368 age-matched and ethnically matched unaffected controls of European-American descent.

Methods: Association analysis of allele and genotype frequencies, determined by TaqMan assays, was performed for the following haplotype-tagging single nucleotide polymorphisms (htSNPs): risk alleles in the complement factor H (CFH) gene (Y402H and IVS14) in the ARMS2/HTRA1 locus on 10q26 (A69S) and protective alleles in CFH (IVS1 and IVS6) and in the complement factor B/complement component C2 (CFB/C2) locus (IVS10 and H9L).

Main outcome measures: Allele and genotype frequencies of the htSNPs in the CFH, CFB/C2, and ARMS2/HTRA1 loci.

Results: Four AMD-associated haplotype-tagging alleles (rs547154, rs1061170, rs1410996, rs10490924) in the 3 major loci, CFH, CFB/C2, and ARMS2/HTRA1, also were statistically significantly associated with the PCV phenotype (P<0.05). Three other alleles from the same loci (rs4151667, rs529825, rs3766404) showed a trend toward association (P<0.2) but did not reach statistical significance, possibly because of the combined effects of a relatively small sample size and low minor allele frequency in the screened populations.

Conclusions: The PCV phenotype in Caucasian patients is associated with the major alleles/genotypes in the AMD-associated loci, suggesting that PCV and AMD are genetically similar in the tested loci.

Publication types

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

MeSH terms

  • Aged
  • Case-Control Studies
  • Choroid / blood supply*
  • Choroid Diseases / diagnosis
  • Choroid Diseases / genetics*
  • Complement C2 / genetics
  • Complement Factor B / genetics
  • Complement Factor H / genetics
  • Complement System Proteins / genetics*
  • Cross-Sectional Studies
  • Female
  • Fluorescein Angiography
  • Gene Expression Profiling
  • Gene Frequency
  • Genotype
  • High-Temperature Requirement A Serine Peptidase 1
  • Humans
  • Indocyanine Green
  • Macular Degeneration / diagnosis
  • Macular Degeneration / genetics*
  • Male
  • Peripheral Vascular Diseases / diagnosis
  • Peripheral Vascular Diseases / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics*
  • Serine Endopeptidases / genetics
  • White People / genetics

Substances

  • ARMS2 protein, human
  • CFH protein, human
  • Complement C2
  • Proteins
  • Complement Factor H
  • Complement System Proteins
  • High-Temperature Requirement A Serine Peptidase 1
  • HTRA1 protein, human
  • Serine Endopeptidases
  • Complement Factor B
  • Indocyanine Green