Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration.
OBJECTIVE
To determine whether there is an association between complement factor H (CFH), high-temperature requirement A-1 (HTRA1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) genotypes and response to treatment with photodynamic therapy (PDT) for age-related macular degeneration (AMD) in a Japanese population.


METHODS
Prospective, case-control study.


METHODS
One hundred ten patients with exudative AMD treated by verteporfin PDT were recruited prospectively at the Department of Ophthalmology, Saitama Medical University Hospital, Saitama, Japan.


METHODS
The patients were genotyped for 4 single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the CFH gene, a rs11200638-SNP in the HTRA1 gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the VEGF gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the PEDF gene using a TaqMan assay.


METHODS
The treatment outcomes and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms.


RESULTS
Best-corrected visual acuity 1 year after PDT was significantly increased in patients with the HTRA1-rs11200638 GG genotype as compared with patients with the GA or AA genotypes (P = 2.9 × 10⁻², 7.0 × 10⁻⁴, respectively). The rate of recurrence in the 12-month period after PDT was also associated with HTRA1-rs11200638 genotype (P = 3.12 × 10⁻²). Patients with the AA genotype of HTRA1-rs11200638 had an approximately 6-fold greater risk of the recurrence than patients with the GG genotype (P = 5.58 × 10⁻³). Significant differences were demonstrated in the mean time interval from the initial treatment to the time of recurrence for the genotypes of CFH-rs1410996/-rs2274700 (P = 8.50 × 10⁻³).


CONCLUSIONS
The HTRA1-rs11200638 and CFH-rs1410996/-rs2274700 variants were associated with response to PDT in this study population. These variants may be used for genetic biomarkers to estimate visual outcomes and recurrences in the response to PDT with significant predictive power.
Tsuchihashi
Takashi
T
Department of Ophthalmology, Saitama Medical University, Iruma, Saitama, Japan.
Mori
Keisuke
K
Horie-Inoue
Kuniko
K
Gehlbach
Peter L
PL
Kabasawa
Sho
S
Takita
Hiroyasu
H
Ueyama
Kazuhiro
K
Okazaki
Yasushi
Y
Inoue
Satoshi
S
Awata
Takuya
T
Katayama
Shigehiro
S
Yoneya
Shin
S
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011166:Porphyrins / Q000627:therapeutic use; D011446:Prospective Studies; D012697:Serine Endopeptidases / Q000235:genetics*; D015843:Serpins / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D000077362:Verteporfin; D014792:Visual Acuity / Q000502:physiology; D000099174:Pigment Epithelium-Derived Factor
D017242:Complement Factor H; D005136:Eye Proteins; D000074289:High-Temperature Requirement A Serine Peptidase 1; D009414:Nerve Growth Factors; D017319:Photosensitizing Agents; D011166:Porphyrins; D012697:Serine Endopeptidases; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000077362:Verteporfin; D000099174:Pigment Epithelium-Derived Factor; C493495:CFH protein, human; C467484:VEGFA protein, human; C474012:HTRA1 protein, human