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

Yasuhiro Ohkuma; Takaaki Hayashi; Tsutomu Sakai; Akira Watanabe; Hisashi Yamada; Masakazu Akahori; Takeshi Itabashi; Takeshi Iwata; Toru Noda; Hiroshi Tsuneoka

doi:10.2147/OPTH.S56483

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

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

Authors

Affiliations

¹ Department of Ophthalmology, Tokyo, Japan.
² Department of Molecular Genetics, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.
³ Division of Molecular and Cellular Biology, National Institute of Sensory Organs, Tokyo, Japan.
⁴ Division of Ophthalmology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

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.