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. 2014:8:143-8.
doi: 10.2147/OPTH.S56483. Epub 2013 Dec 27.

Retinal angiomatous proliferation associated with risk alleles of ARMS2/HTRA1 gene polymorphisms in Japanese patients

Yasuhiro Ohkuma  1 , Takaaki Hayashi  1 , Tsutomu Sakai  1 , Akira Watanabe  1 , Hisashi Yamada  2 , Masakazu Akahori  3 , Takeshi Itabashi  3 , Takeshi Iwata  3 , Toru Noda  4 , Hiroshi Tsuneoka  1
Affiliations

Retinal angiomatous proliferation associated with risk alleles of ARMS2/HTRA1 gene polymorphisms in Japanese patients

Yasuhiro Ohkuma et al. Clin Ophthalmol. 2014.

Abstract

Background: The purpose of this study was to investigate the association between ARMS2/HTRA1, CFH, and C3 gene polymorphisms and retinal angiomatous proliferation (RAP), an infrequent and severe form of exudative age-related macular degeneration, which is characterized by intraretinal neovascularization.

Methods: Diagnosis of RAP was based on fundus photographs, images of fluorescein and indocyanine green angiographies, and optical coherence tomography findings. Six single nucleotide polymorphisms (SNPs), A69S (rs10490924) in ARMS2, rs11200638 in HTRA1, I62V (rs800292) in CFH, Y402H (rs1061170) in CFH, R80G (rs2230199) in C3, and rs2241394 in C3, were genotyped in eight Japanese patients with RAP.

Results: The two SNPs in the ARMS2/HTRA1 were in complete linkage disequilibrium. The frequency of the risk T allele in ARMS2 (the risk A allele in HTRA1) was 93.8% in the RAP patients. The frequency of homozygosity for the risk genotype TT of ARMS2 (the risk genotype AA of HTRA1) was 87.5%. The frequency of the non-risk allele (A) of I62V was 100%. The frequencies of risk alleles of Y402H, R80G, and rs2241394 were 12.5%, 0%, and 18.8%, respectively.

Conclusion: Our results suggest that the risk alleles of the ARMS2/HTRA1 SNPs may be associated with development of RAP and play a major role in the pathogenesis of intraretinal angiogenesis.

Keywords: ARMS2/HTRA1 genes; age-related macular degeneration; components of the complement system; retinal angiomatous proliferation; single nucleotide polymorphisms.

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Figures

Figure 1
Figure 1
Color fundus photographs (A and D), indocyanine green fundus angiographies (B and E), and optical coherence tomography images (C and F) from the right eye (A–C) and the left eye (D–F) of an 83-year-old woman (patient 1). Notes: We diagnosed her right eye with stage II retinal angiomatous proliferation and her left eye with stage III retinal angiomatous proliferation. (A and D) Fundus image shows intraretinal hemorrhages with a large number of soft drusen and pigment epithelial detachment. (B) Indocyanine green fundus angiographies shows some hotspots. One of them connects retinal vessels (arrow), corresponding to the intraretinal neovascularization. (C) A vertical optical coherence tomography image shows a pigment epithelial detachment, cystoid macular edema, and retinal angiomatous proliferation lesion (arrow). (E) Indocyanine green fundus angiographies shows choroidal neovascularization (arrow) that connects retinal vessels, corresponding to retinal-choroidal anastomosis. (F) A vertical optical coherence tomography image shows a pigment epithelial detachment, cystoid macular edema, and a retinal pigment epithelium line that has ruptured (arrow).
See this image and copyright information in PMC

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