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タイトル: A prospective multicenter study on genome wide associations to ranibizumab treatment outcome for age-related macular degeneration
著者: 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  kyouindb  KAKEN_id
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  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-7740-2732 (unconfirmed)
Oishi, Akio  KAKEN_id  orcid https://orcid.org/0000-0002-0977-9458 (unconfirmed)
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  KAKEN_id  orcid https://orcid.org/0000-0002-1587-630X (unconfirmed)
Matsuda, Fumihiko  kyouindb  KAKEN_id
Tsujikawa, Akitaka  kyouindb  KAKEN_id
Negi, Akira
Yoneya, Shin
Iwata, Takeshi
Yoshimura, Nagahisa
著者名の別形: 山城, 健児
吉川, 宗光
三宅, 正裕
仲田, 勇夫
大音, 壮太郎
田村, 寛
大石, 明生
山田, 亮
松田, 文彦
辻川, 明孝
吉村, 長久
キーワード: Macular degeneration
Retinal diseases
発行日: 23-Aug-2017
出版者: Springer Nature
誌名: Scientific Reports
巻: 7
論文番号: 9196
抄録: 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.
著作権等: © The Author(s) 2017
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/231027
DOI(出版社版): 10.1038/s41598-017-09632-0
PubMed ID: 28835685
出現コレクション:学術雑誌掲載論文等

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