IIDA Tomohiro    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Professor and Division head
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	A prospective multicenter study on genome wide associations to ranibizumab treatment outcome for age-related macular degeneration.
Journal	Formal name：Scientific reports Abbreviation：Sci Rep ISSN code：20452322/20452322
Domestic / Foregin	Foregin
Volume, Issue, Page	7(1),pp.9196
Author and coauthor	Yamashiro Kenji, Mori Keisuke, Honda Shigeru, Kano Mariko, Yanagi Yasuo, Obana Akira, Sakurada Yoichi, Sato Taku, Nagai Yoshimi, Hikichi Taiichi, Kataoka Yasushi, Hara Chikako, Koyama Yasurou, Koizumi Hideki, Yoshikawa Munemitsu, Miyake Masahiro, Nakata Isao, Tsuchihashi Takashi, Horie-Inoue Kuniko, Matsumiya Wataru, Ogasawara Masashi, Obata Ryo, Yoneyama Seigo, Matsumoto Hidetaka, Ohnaka Masayuki, Kitamei Hirokuni, Sayanagi Kaori, Ooto Sotaro, Tamura Hiroshi, Oishi Akio, Kabasawa Sho, Ueyama Kazuhiro, Miki Akiko, Kondo Naoshi, Bessho Hiroaki, Saito Masaaki, Takahashi Hidenori, Tan Xue, Azuma Keiko, Kikushima Wataru, Mukai Ryo, Ohira Akihiro, Gomi Fumi, Miyata Kazunori, Takahashi Kanji, Kishi Shoji, Iijima Hiroyuki, Sekiryu Tetsuju, Iida Tomohiro, Awata Takuya, Inoue Satoshi, Yamada Ryo, Matsuda Fumihiko, Tsujikawa Akitaka, Negi Akira, Yoneya Shin, Iwata Takeshi, Yoshimura Nagahisa
Publication date	2017/08
Summary	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.
DOI	10.1038/s41598-017-09632-0
PMID	28835685