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

Abstract

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.

• Authors: Kenji Yamashiro, Keisuke Mori, Shigeru Honda, Mariko Kano, Yasuo Yanagi, Akira Obana, Yoichi Sakurada, Taku Sato, Yoshimi Nagai, Taiichi Hikichi, Yasushi Kataoka, Chikako Hara, Yasurou Koyama, Hideki Koizumi, Munemitsu Yoshikawa, Masahiro Miyake, Isao Nakata, Takashi Tsuchihashi, Kuniko Horie-Inoue, Wataru Matsumiya, Masashi Ogasawara, Ryo Obata, Seigo Yoneyama, Hidetaka Matsumoto, Masayuki Ohnaka, Hirokuni Kitamei, Kaori Sayanagi, Sotaro Ooto, Hiroshi Tamura, Akio Oishi, Sho Kabasawa, Kazuhiro Ueyama, Akiko Miki, Naoshi Kondo, Hiroaki Bessho, Masaaki Saito, Hidenori Takahashi, Xue Tan, Keiko Azuma, Wataru Kikushima, Ryo Mukai, Akihiro Ohira, Fumi Gomi, Kazunori Miyata, Kanji Takahashi, Shoji Kishi, Hiroyuki Iijima, Tetsuju Sekiryu, Tomohiro Iida, Takuya Awata, Satoshi Inoue, Ryo Yamada, Fumihiko Matsuda, Akitaka Tsujikawa, Akira Negi, Shin Yoneya, Takeshi Iwata, Nagahisa Yoshimura
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 9196 (08 23 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28835685 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Genetic Markers
• Ranibizumab

Topics

• Aged
• Aged, 80 and over
• Alleles
• Angiogenesis Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Female
• Genetic Markers
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Macular Degeneration (diagnosis, drug therapy, genetics)
• Male
• Middle Aged
• Odds Ratio
• Polymorphism, Single Nucleotide
• Ranibizumab (administration & dosage, adverse effects, therapeutic use)
• Severity of Illness Index
• Treatment Outcome
• Visual Acuity