Association of pattern dystrophy with an HTRA1 single-nucleotide polymorphism

Arch Ophthalmol. 2012 Aug;130(8):987-91. doi: 10.1001/archophthalmol.2012.1483.


Objective: To evaluate if adult-onset foveomacular vitelliform dystrophy (AOFVD) and butterfly-shaped pigment dystrophy (BSPD) are associated with risk single-nucleotide polymorphisms (SNPs) for age-related macular degeneration (AMD).

Methods: This was a tertiary referral center-based cross-sectional study including 35 consecutive patients with BSPD and AOFVD, 317 patients with AMD, and 159 unaffected individuals. Demographics, clinical information, and ophthalmic imaging studies were collected. Sequencing was performed for the peripherin/RDS and BEST1 genes, and genotyping was performed for SNPs in the genes for complement factor H (CFH) (rs1061170), HTRA1 (rs11200638), and complement component 3 (C3) (rs2231099).

Results: Adult-onset foveomacular vitelliform dystrophy and BSPD were diagnosed in 24 (68.6%) and 11 (31.4%) of the 35 patients, respectively. The mean (SD) age of patients with pattern dystrophy (PD) was 75.3 (10) years and median visual acuity was 0.7. Pattern dystrophy was associated with the HTRA1 risk allele compared with unaffected individuals (odds ratio, 1.72; 95% CI, 1.11-2.66; P = .03). The HTRA1 SNP showed similar prevalence in patients with AMD and PD. The CFH risk allele was significantly less common in patients with PD compared with patients with AMD (odds ratio, 0.47; 95% CI, 0.28-0.76; P = .002). No mutations in peripherin/RDS or BEST1 were detected.

Conclusions: The AOFVD and BSPD phenotypes are associated with an HTRA1 risk SNP. These phenotypes often present in elderly individuals who do not carry peripherin/RDS gene mutations and are associated with retinal pigment epithelium alterations and increased risk for choroidal neovascularization. Further research is required to evaluate if AOFVD and BSPD phenotypes in aged individuals are associated with AMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bestrophins
  • Chloride Channels / genetics
  • Complement Factor H / genetics
  • Cross-Sectional Studies
  • Eye Proteins / genetics
  • Female
  • Fluorescein Angiography
  • Genotype
  • High-Temperature Requirement A Serine Peptidase 1
  • Humans
  • Intermediate Filament Proteins / genetics
  • Male
  • Membrane Glycoproteins / genetics
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Peripherins
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Retinal Dystrophies / diagnosis
  • Retinal Dystrophies / genetics*
  • Risk Factors
  • Serine Endopeptidases / genetics*
  • Tomography, Optical Coherence
  • Vitelliform Macular Dystrophy / diagnosis
  • Vitelliform Macular Dystrophy / genetics*


  • BEST1 protein, human
  • Bestrophins
  • CFH protein, human
  • Chloride Channels
  • Eye Proteins
  • Intermediate Filament Proteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • PRPH protein, human
  • PRPH2 protein, human
  • Peripherins
  • Complement Factor H
  • High-Temperature Requirement A Serine Peptidase 1
  • HtrA1 protein, human
  • Serine Endopeptidases

Supplementary concepts

  • Patterned dystrophy of retinal pigment epithelium