Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration

Takashi Tsuchihashi, Keisuke Mori, Kuniko Horie-Inoue, Peter Gehlbach, Sho Kabasawa, Hiroyasu Takita, Kazuhiro Ueyama, Yasushi Okazaki, Satoshi Inoue, Takuya Awata, Shigehiro Katayama, Shin Yoneya

Research output: Contribution to journalArticle

Abstract

Purpose: 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. Design: Prospective, case-control study. Participants: 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. Main Outcome Measures: 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. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Original languageEnglish (US)
Pages (from-to)93-100
Number of pages8
JournalOphthalmology
Volume118
Issue number1
DOIs
StatePublished - Jan 2011

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Complement Factor H
Macular Degeneration
Photochemotherapy
Genotype
Temperature
Single Nucleotide Polymorphism
Vascular Endothelial Growth Factor A
Recurrence
Therapeutics
Genes
Disclosure
Ophthalmology
Population
Visual Acuity
Case-Control Studies
Japan
Biomarkers
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Ophthalmology

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Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration. / Tsuchihashi, Takashi; Mori, Keisuke; Horie-Inoue, Kuniko; Gehlbach, Peter; Kabasawa, Sho; Takita, Hiroyasu; Ueyama, Kazuhiro; Okazaki, Yasushi; Inoue, Satoshi; Awata, Takuya; Katayama, Shigehiro; Yoneya, Shin.

In: Ophthalmology, Vol. 118, No. 1, 01.2011, p. 93-100.

Research output: Contribution to journalArticle

Tsuchihashi, T, Mori, K, Horie-Inoue, K, Gehlbach, P, Kabasawa, S, Takita, H, Ueyama, K, Okazaki, Y, Inoue, S, Awata, T, Katayama, S & Yoneya, S 2011, 'Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration', Ophthalmology, vol. 118, no. 1, pp. 93-100. https://doi.org/10.1016/j.ophtha.2010.04.007
Tsuchihashi, Takashi ; Mori, Keisuke ; Horie-Inoue, Kuniko ; Gehlbach, Peter ; Kabasawa, Sho ; Takita, Hiroyasu ; Ueyama, Kazuhiro ; Okazaki, Yasushi ; Inoue, Satoshi ; Awata, Takuya ; Katayama, Shigehiro ; Yoneya, Shin. / Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration. In: Ophthalmology. 2011 ; Vol. 118, No. 1. pp. 93-100.
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T1 - Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration

AU - Tsuchihashi, Takashi

AU - Mori, Keisuke

AU - Horie-Inoue, Kuniko

AU - Gehlbach, Peter

AU - Kabasawa, Sho

AU - Takita, Hiroyasu

AU - Ueyama, Kazuhiro

AU - Okazaki, Yasushi

AU - Inoue, Satoshi

AU - Awata, Takuya

AU - Katayama, Shigehiro

AU - Yoneya, Shin

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N2 - Purpose: 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. Design: Prospective, case-control study. Participants: 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. Main Outcome Measures: 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. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

AB - Purpose: 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. Design: Prospective, case-control study. Participants: 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. Main Outcome Measures: 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. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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