Elsevier

Ophthalmology

Volume 117, Issue 8, August 2010, Pages 1567-1570
Ophthalmology

Original article
Three Major Loci Involved in Age-Related Macular Degeneration Are Also Associated with Polypoidal Choroidal Vasculopathy

https://doi.org/10.1016/j.ophtha.2009.12.018Get rights and content

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.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Materials and Methods

The PCV cohort corresponded to 55 consecutive patients of Caucasian descent who were referred to 2 ophthalmologic centers (Edward Harkness Eye Institute, Columbia University, and The Vitreous, Retina, Macula Consultants of New York) during a 2-year interval (from November 5, 2006, to December 27, 2008) and enrolled after giving informed consent. The principles outlined in the Declaration of Helsinki were followed, and an institutional review board approval was obtained specifically for this

Results

All study subjects (55) with PCV were not related to each other and of European-American descent with an approximate 2:1 male to female ratio (32/55 [60%] were male). The average (standard deviation) age at the time of enrollment in the study was 73 (±8.2) years.

Genotype and allele frequencies of the 7 haplotype-tagging single nucleotide polymorphisms (SNPs) from CFH (4), ARMS2 (1), and CFB/C2 (2) loci in 55 patients with PCV were analyzed and compared with the same data acquired previously on

Discussion

The current study showed that the allele frequencies in Caucasian patients with PCV are in good correlation with the data in patients with AMD in the 3 loci. Four AMD-associated alleles (rs547154, rs1061170, rs1410996, rs10490924) in the 3 major loci, CFH, CFB/C2, and ARMS2/HTRA1, also were significantly associated with the PCV phenotype (P<0.05), and the other 3 tested SNPs (rs4151667, rs529825, rs3766404) demonstrated a tendency toward correlation (P<0.2). Therefore, common genetic variation

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    • Cited by (0)

    Manuscript no. 2009-1288.

    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    Supported by grants National Institutes of HealthEY13435, EY017404, The Macula Foundation, Inc., and an unrestricted grant to the Department of Ophthalmology, Columbia University, from Research to Prevent Blindness, Inc. Dr. Imamura was funded by grants from Koureisha Ganshikkan Kenkyu Zaidan, Mishima Saiichi-kinen Gankakenkyu Kokusaikouryu Kikin, and Takeda Kagaku Shinkou Zaidan.

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