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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