Association of pattern dystrophy with an HTRA1 single-nucleotide polymorphism

Area of Science:

• Ophthalmology
• Genetics
• Retinal Diseases

Background:

• Adult-onset foveomacular vitelliform dystrophy (AOFVD) and butterfly-shaped pigment dystrophy (BSPD) are distinct retinal conditions.
• Their genetic associations, particularly with age-related macular degeneration (AMD) risk single-nucleotide polymorphisms (SNPs), are not fully understood.

Purpose of the Study:

• To investigate the association between AOFVD and BSPD and known AMD risk SNPs.
• To determine if these pattern dystrophies share genetic risk factors with AMD.

Main Methods:

• Cross-sectional study of 35 patients with AOFVD/BSPD, 317 with AMD, and 159 controls.
• Genotyping for CFH (rs1061170), HTRA1 (rs11200638), and C3 (rs2231099) SNPs.
• Sequencing of peripherin/RDS and BEST1 genes.

Main Results:

• AOFVD and BSPD were diagnosed in 35 patients (mean age 75.3 years).
• The HTRA1 risk allele was associated with pattern dystrophy (PD) (OR, 1.72; P = .03) and showed similar prevalence in AMD and PD.
• The CFH risk allele was less common in PD than in AMD (OR, 0.47; P = .002). No mutations in peripherin/RDS or BEST1 were found.

Conclusions:

• AOFVD and BSPD phenotypes are associated with the HTRA1 risk SNP.
• These conditions in elderly individuals, without peripherin/RDS mutations, suggest RPE alterations and increased risk for choroidal neovascularization.
• Further research is needed to clarify the relationship between these phenotypes and AMD.