4 years ago

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

Akihiro Ohira, Hidenori Takahashi, Wataru Matsumiya, Keiko Azuma, Seigo Yoneyama, Masaaki Saito, Kazunori Miyata, Hiroshi Tamura, Hirokuni Kitamei, Masashi Ogasawara, Tomohiro Iida, Taku Sato, Shoji Kishi, Sho Kabasawa, Kenji Yamashiro, Ryo Obata, Yoichi Sakurada, Akira Obana, Masahiro Miyake, Tetsuju Sekiryu, Shigeru Honda, Takuya Awata, Hideki Koizumi, Chikako Hara, Akiko Miki, Hidetaka Matsumoto, Yoshimi Nagai, Nagahisa Yoshimura, Takeshi Iwata, Wataru Kikushima, Mariko Kano, Naoshi Kondo, Kuniko Horie-Inoue, Yasurou Koyama, Yasushi Kataoka, Taiichi Hikichi, Sotaro Ooto, Munemitsu Yoshikawa, Yasuo Yanagi, Hiroaki Bessho, Kazuhiro Ueyama, Fumi Gomi, Akio Oishi, Ryo Mukai, Masayuki Ohnaka, Akira Negi, Kanji Takahashi, Ryo Yamada, Shin Yoneya, Fumihiko Matsuda, Isao Nakata, Takashi Tsuchihashi, Keisuke Mori, Xue Tan, Kaori Sayanagi, Akitaka Tsujikawa, Satoshi Inoue, Hiroyuki Iijima
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.

Publisher URL: https://www.nature.com/articles/s41598-017-09632-0

DOI: 10.1038/s41598-017-09632-0

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