Scientific Reports (Aug 2017)
A prospective multicenter study on genome wide associations to ranibizumab treatment outcome for age-related macular degeneration
- Kenji Yamashiro,
- Keisuke Mori,
- Shigeru Honda,
- Mariko Kano,
- Yasuo Yanagi,
- Akira Obana,
- Yoichi Sakurada,
- Taku Sato,
- Yoshimi Nagai,
- Taiichi Hikichi,
- Yasushi Kataoka,
- Chikako Hara,
- Yasurou Koyama,
- Hideki Koizumi,
- Munemitsu Yoshikawa,
- Masahiro Miyake,
- Isao Nakata,
- Takashi Tsuchihashi,
- Kuniko Horie-Inoue,
- Wataru Matsumiya,
- Masashi Ogasawara,
- Ryo Obata,
- Seigo Yoneyama,
- Hidetaka Matsumoto,
- Masayuki Ohnaka,
- Hirokuni Kitamei,
- Kaori Sayanagi,
- Sotaro Ooto,
- Hiroshi Tamura,
- Akio Oishi,
- Sho Kabasawa,
- Kazuhiro Ueyama,
- Akiko Miki,
- Naoshi Kondo,
- Hiroaki Bessho,
- Masaaki Saito,
- Hidenori Takahashi,
- Xue Tan,
- Keiko Azuma,
- Wataru Kikushima,
- Ryo Mukai,
- Akihiro Ohira,
- Fumi Gomi,
- Kazunori Miyata,
- Kanji Takahashi,
- Shoji Kishi,
- Hiroyuki Iijima,
- Tetsuju Sekiryu,
- Tomohiro Iida,
- Takuya Awata,
- Satoshi Inoue,
- Ryo Yamada,
- Fumihiko Matsuda,
- Akitaka Tsujikawa,
- Akira Negi,
- Shin Yoneya,
- Takeshi Iwata,
- Nagahisa Yoshimura
Affiliations
- Kenji Yamashiro
- Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine
- Keisuke Mori
- Department of Ophthalmology, Saitama Medical University
- Shigeru Honda
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine
- Mariko Kano
- Department of Ophthalmology, Fukushima Medical University School of Medicine
- Yasuo Yanagi
- Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
- Akira Obana
- Department of Ophthalmology, Seirei Hamamatsu General Hospital
- Yoichi Sakurada
- Department of Ophthalmology, Faculty of Medicine, University of Yamanashi
- Taku Sato
- Department of Ophthalmology, Gunma University School of Medicine
- Yoshimi Nagai
- Department of Ophthalmology, Kansai Medical University
- Taiichi Hikichi
- Ohtsuka Eye Hospital
- Yasushi Kataoka
- Miyata Ophthalmic Hospital
- Chikako Hara
- Department of Ophthalmology, Osaka University Graduate School of Medicine
- Yasurou Koyama
- Department of Ophthalmology, Shimane University Faculty of Medicine
- Hideki Koizumi
- Department of Ophthalmology, Tokyo Women’s Medical University, School of Medicine
- Munemitsu Yoshikawa
- Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine
- Masahiro Miyake
- Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine
- Isao Nakata
- Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine
- Takashi Tsuchihashi
- Department of Ophthalmology, Saitama Medical University
- Kuniko Horie-Inoue
- Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University
- Wataru Matsumiya
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine
- Masashi Ogasawara
- Department of Ophthalmology, Fukushima Medical University School of Medicine
- Ryo Obata
- Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
- Seigo Yoneyama
- Department of Ophthalmology, Faculty of Medicine, University of Yamanashi
- Hidetaka Matsumoto
- Department of Ophthalmology, Gunma University School of Medicine
- Masayuki Ohnaka
- Department of Ophthalmology, Kansai Medical University
- Hirokuni Kitamei
- Ohtsuka Eye Hospital
- Kaori Sayanagi
- Hikichi Eye Clinic
- Sotaro Ooto
- Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine
- Hiroshi Tamura
- Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine
- Akio Oishi
- Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine
- Sho Kabasawa
- Department of Ophthalmology, Saitama Medical University
- Kazuhiro Ueyama
- Department of Ophthalmology, Saitama Medical University
- Akiko Miki
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine
- Naoshi Kondo
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine
- Hiroaki Bessho
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine
- Masaaki Saito
- Department of Ophthalmology, Fukushima Medical University School of Medicine
- Hidenori Takahashi
- Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
- Xue Tan
- Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
- Keiko Azuma
- Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
- Wataru Kikushima
- Department of Ophthalmology, Faculty of Medicine, University of Yamanashi
- Ryo Mukai
- Department of Ophthalmology, Gunma University School of Medicine
- Akihiro Ohira
- Department of Ophthalmology, Shimane University Faculty of Medicine
- Fumi Gomi
- Department of Ophthalmology, Osaka University Graduate School of Medicine
- Kazunori Miyata
- Miyata Ophthalmic Hospital
- Kanji Takahashi
- Department of Ophthalmology, Kansai Medical University
- Shoji Kishi
- Department of Ophthalmology, Gunma University School of Medicine
- Hiroyuki Iijima
- Department of Ophthalmology, Faculty of Medicine, University of Yamanashi
- Tetsuju Sekiryu
- Department of Ophthalmology, Fukushima Medical University School of Medicine
- Tomohiro Iida
- Department of Ophthalmology, Tokyo Women’s Medical University, School of Medicine
- Takuya Awata
- Department of Diabetes, Endocrinology and Metabolism, International University of Health and Welfare Hospital
- Satoshi Inoue
- Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University
- Ryo Yamada
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine
- Fumihiko Matsuda
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine
- Akitaka Tsujikawa
- Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine
- Akira Negi
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine
- Shin Yoneya
- Department of Ophthalmology, Saitama Medical University
- Takeshi Iwata
- Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center
- Nagahisa Yoshimura
- Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine
- DOI
- https://doi.org/10.1038/s41598-017-09632-0
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 8
Abstract
Abstract We conducted a genome-wide association study (GWAS) on the outcome of anti-VEGF treatment for exudative age-related macular degeneration (AMD) in a prospective cohort. Four hundred and sixty-one treatment-naïve AMD patients were recruited at 13 clinical centers and all patients were treated with 3 monthly injections of ranibizumab followed by pro re nata regimen treatment for one year. Genomic DNA was collected from all patients for a 2-stage GWAS on achieving dry macula after the initial treatment, the requirement for an additional treatment, and visual acuity changes during the 12-month observation period. In addition, we evaluated 9 single-nucleotide polymorphisms (SNPs) in 8 previously reported AMD-related genes for their associations with treatment outcome. The discovery stage with 256 patients evaluated 8,480,849 SNPs, but no SNPs showed genome-wide level significance in association with treatment outcomes. Although SNPs with P-values of <5 × 10−6 were evaluated in replication samples of 205 patients, no SNP was significantly associated with treatment outcomes. Among AMD-susceptibility genes, rs10490924 in ARMS2/HTRA1 was significantly associated with additional treatment requirement in the discovery stage (P = 0.0023), and pooled analysis with the replication stage further confirmed this association (P = 0.0013). ARMS2/HTRA1 polymorphism might be able to predict the frequency of injection after initial ranibizumab treatment.
