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


METHODS
A case-control study.


METHODS
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.


METHODS
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 = 1.24x10(-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 = 2.36x10(-5), 7.18x10(-5), 7.18x10(-5), 2.70x10(-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.
Mori
Keisuke
K
Department of Ophthalmology, Saitama Medical University, Iruma, Saitama, Japan. keisuke@saitama-med.ac.jp
Horie-Inoue
Kuniko
K
Gehlbach
Peter L
PL
Takita
Hiroyasu
H
Kabasawa
Sho
S
Kawasaki
Izumi
I
Ohkubo
Tomoko
T
Kurihara
Susumu
S
Iizuka
Hiroyuki
H
Miyashita
Yumi
Y
Katayama
Shigehiro
S
Awata
Takuya
T
Yoneya
Shin
S
Inoue
Satoshi
S
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004396:Coloring Agents; D017242:Complement Factor H / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007208:Indocyanine Green; D007564:Japan; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012697:Serine Endopeptidases / Q000235:genetics*; D015843:Serpins / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D000099174:Pigment Epithelium-Derived Factor
D004396:Coloring Agents; D017242:Complement Factor H; D005136:Eye Proteins; D000074289:High-Temperature Requirement A Serine Peptidase 1; D007208:Indocyanine Green; D009414:Nerve Growth Factors; D012697:Serine Endopeptidases; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C493495:CFH protein, human; C467484:VEGFA protein, human; C474012:HTRA1 protein, human