Journal Article A prospective multicenter study on genome wide associations to ranibizumab treatment outcome for age-related macular degeneration

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

7p.9196 , 2017-08-23 , Nature Publishing Group
ISSN:2045232220452322
Description
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 sixtyone 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 x 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.
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