Phenotype and Genotype Characteristics of Age-related Macular Degeneration in a Japanese Population

Received 13 June 2009; received in revised form 26 September 2009; accepted 1 October 2009. published online 04 February 2010.
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Purpose

To describe phenotype and genotype characteristics of age-related macular degeneration (AMD) in Japanese patients.

Design

A case-control study.

Participants

A total of 550 case-control samples composed of 408 consecutive AMD cases and 142 controls.

Methods

Clinical information assessing age, gender, affected eyes, fundus features, and fluorescein/indocyanine green angiograms were systematically evaluated. Four single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the complement factor H (CFH) gene, 1 SNP (rs11200638) in the high-temperature requirement factor A1 (HTRA1) gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were assessed using TaqMan technology.

Main Outcome Measures

The clinical phenotype information and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms.

Results

Of Japanese patients with neovascular AMD (nAMD), 219 (58.7%) had typical nAMD and 154 (41.3%) had polypoidal choroidal vasculopathy (PCV). The frequency of bilateral exudative involvement was similar between typical nAMD (15.5%) and PCV (13.6%) (P = 0.613). Significant soft drusen were observed in the fellow eyes of 88 (47.6%) of 185 patients with unilateral typical nAMD and in 25 (18.8%) of 133 patients with unilateral PCV (P = 1.24×10−7). A serous pigment epithelium detachment was seen in 55 (25.1%) of 219 patients with typical nAMD and in 64 (41.6%) of 154 patients with PCV. A significant association was noted in CFH-rs800292, CFH-rs1410996, CFH-rs2274700, and HTRA1-rs11200638 with AMD development (P = 2.36×10−5, 7.18×10−5, 7.18×10−5, 2.70×10−7, respectively; population attributable risk = 57.3%, 57.8%, 57.8%, and 58.9%, respectively). We estimated the highest-risk group to have an approximately 70-fold greater risk of nAMD compared with the lowest-risk group when analyzing a combination of 4 SNPs in the CFH and HTRA1 genes.

Conclusions

The Japanese AMD phenotype is characterized by a higher frequency of PCV, male predominance, and lower frequency of bilateral presentation compared with Caucasian AMD. Genotype analyses demonstrate a significant population attributable risk for SNPs in the CFH and HTRA1 genes and demonstrate joint effects for both genes. Gene variants in both CFH and HTRA1 contribute significantly to the AMD phenotype in a Japanese population.

Financial Disclosure(s)

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

1 Department of Ophthalmology, Saitama Medical University, Iruma, Saitama, Japan

2 Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Iruma, Saitama, Japan

3 Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical University, Iruma, Saitama, Japan

4 Division of RI Laboratory, Biomedical Research Center, Saitama Medical University, Iruma, Saitama, Japan

5 Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland

Correspondence Keisuke Mori, MD, PhD, Department of Ophthalmology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma, Saitama, 350-0495, Japan

Manuscript no. 2009-806.

Available online: •••.

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

Financial Support: This research was supported in part by a Grant from the Eye Research Foundation for the Aged (KM), Institutional Grant from the Medical Research Center, Saitama Medical University (#20-1-2-02, KM) and a grant-in-aid (C-21592242) from the Ministry of Education, Science and Culture, Tokyo, Japan.

⁎ These authors contributed equally to this manuscript.

PII: S0161-6420(09)01172-5

doi:10.1016/j.ophtha.2009.10.001