Establishment of diagnostic markers for recuccent stone disease by genome-wide associated analysis.

• Project/Area Number: 26462450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: KANEMOTO Kazuhiro 名古屋市立大学, 大学院医学研究科, 研究員 (30381825)
• Co-Investigator(Kenkyū-buntansha): 郡 健二郎 名古屋市立大学, その他部局等, 学長 (30122047) ; 安藤 亮介 名古屋市立大学, 大学院医学研究科, 助教 (30381867) ; 戸澤 啓一 名古屋市立大学, 大学院医学研究科, 准教授 (40264733) ; 安井 孝周 名古屋市立大学, 大学院医学研究科, 教授 (40326153) ; 岡田 淳志 名古屋市立大学, 大学院医学研究科, 講師 (70444966)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 尿路結石 / ゲノムワイド関連解析 / マルチプレックス解析 / 炎症 / マクロファージ / リスク因子 / 結石消失 / ケモカイン / サイトカイン / SNP / ゲノムワイド解析

Outline of Final Research Achievements

We have conducted large-scale screening focusing on single nucleotide polymorphisms (SNPs), identified multiple urinary calculi related regions on the genome, and reported the association with onset risk. In this study, we performed (1) haplotype analysis of the related genes based on the results of genome-wide association analysis, and (2) multiplex analysis for kidney stone-related urinary markers between kidney stones and healthy subjects.
As a result, we identified 5q 35.3, 7 p 14. 3 and 13 q 14. 1 areas related to stone formation and found that the odds ratio increased with the number of risk allele . In addition, urinary IL-1a and IL-4 were identified as the factors to discriminate normal subjects from calculus patients (especially initial stone formers) by multiplex analysis of urinary inflammation-related factors.

Research Products

• [Journal Article] Genomic landscape of experimental bladder cancer in rodents and its application to human bladder cancer: gene amplification and potential overexpression of Cyp2a5/CYP2A6 are associated with the invasive phenotype. (2016)
  • Author(s): Kanemoto Kazuhiro, Fukuta Katsuhiro, Kawai Noriyasu, Tozawa Keiichi, Ochiai Masako, Okamoto Koji, Ohnami Sumiko, Sakamoto Hiromi, Yoshida Teruhiko, Kanai Yae, Katoh Masaru, Yasui Takahiro, Kohri Kenjiro, Kakizoe Tadao, Nakagama Hitoshi
  • Journal Title: PLoS One Volume: 30 Issue: 11 Pages: e0167374-e0167374
  • DOI: 10.1371/journal.pone.0167374
  • Peer Reviewed / Open Access
• [Presentation] The effect of green tea for the early period of renal crystal formation. (2016)
  • Author(s): Hirose Masahito, Unno Rei, Banno Rika, Taguchi Kazumi, Fujii Yasuhiro, Hamamoto Shuzo, Kanemoto Kazuhiro, Okada Atsushi, Sakakura Takeshi, Tozawa Keiichi, Kohri Kenjiro, Yasui Takahiro
  • Organizer: 13th International Symposium on Urolithiasis
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
  • Year and Date: 2016-07-19
  • Int'l Joint Research
• [Presentation] 尿道ステントMemokath(R)留置後に発生した結石の臨床的検討 (2016)
  • Author(s): 広瀬 真仁、阪野 里花、濵本 周造、安藤 亮介、金本 一洋、岡田 淳志、坂倉 毅、戸澤 啓一、安井 孝周
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台国際センター 他（宮城県仙台市）
  • Year and Date: 2016-04-23
• [Presentation] Cyp2a5/CY2A6遺伝子の増幅と過剰発現は筋層浸潤膀胱がんの発生早期に関与している (2016)
  • Author(s): 金本 一洋、阪野 里花、廣瀬 真仁、坂倉 毅、福田 勝洋、山田 健司、梅本 幸裕、河合 憲康、戸澤 啓一、加藤 勝、金井 弥栄、中釜 斉、安井 孝周
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台国際センター 他（宮城県仙台市）
  • Year and Date: 2016-04-23
• [Presentation] 内鼠径ヘルニアを合併した陰嚢脱分化型脂肪肉腫の1例 (2016)
  • Author(s): 山田 健司、海野 奈央子、金本 一洋、橋本 良博、岩瀬 豊
  • Organizer: 第272回日本泌尿器科学会東海地方会
  • Place of Presentation: KDX桜通ビル（愛知県名古屋市）
• [Presentation] TUL施行後短期間で珊瑚状結石を生じた1例 (2016)
  • Author(s): 海野 奈央子、山田 健司、金本 一洋、橋本 良博、岩瀬 豊
  • Organizer: 第273回日本泌尿器科学会東海地方会
  • Place of Presentation: KDX桜通ビル（愛知県名古屋市）
• [Presentation] Three novel loci associated with susceptibility to urolithiasis from a genome-wide association study: A case-control association study. (2014)
  • Author(s): Yasui Takahiro, Okada Atsushi, Usami Masayuki, Hamamoto Shuzo, Ando Ryosuke, Itoh Yasunori, Tozawa Keiichi, Sasaki Shoichi, Hayashi Yutaro, Sato Yoshikazu, Higashi Yoshihito, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2014
  • Place of Presentation: Orlando (USA)
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Possible new urine markers for calcium oxalate “stone formers”: macrophage-related cytokines/chemokines detected by multiplex analysis. (2014)
  • Author(s): Okada Atsushi, Yasui Takahiro, Taguchi Kazumi, Fujii Yasuhiro, Niimi Kazuhiro, Hamamoto Shuzo, Hirose Masahito, Ando Ryosuke, Kubota Yasue, Itoh Yasunori, Tozawa Keiichi, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2014
  • Place of Presentation: Orlando (USA)
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] ゲノムワイド関連解析による尿路結石リスク診断法の開発 (2014)
  • Author(s): 安井 孝周、岡田 淳志、宇佐美 雅之、田口 和己、廣瀬 泰彦、新美 和寛、濵本 周造、安藤 亮介、伊藤 恭典、戸澤 啓一、東 義人、佐藤 嘉一、郡 健二郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県、神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] マルチプレックス解析を用いた尿路結石患者に特異的な尿中マクロファージ関連因子の同定 (2014)
  • Author(s): 岡田 淳志、田口 和己、藤井 泰普、新美 和寛、濵本 周造、安井 孝周、広瀬 真仁、戸澤 啓一、郡 健二郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県、神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] Three novel susceptibility loci identified from a genome-wide association study (GWAS) are associated with urolithiasis risk. (2014)
  • Author(s): Yasui Takahiro, okada Atsushi, Usami Masayuki, Hamamoto Shuzo, Ando Ryosuke, Itoh Yasunori, Sasaki Shoichi, Hayashi Yutaro, Higashi Yoshihito, Sato Yoshikazu, Kohri Kenjiro
  • Organizer: 29th Annual EAU Congress
  • Place of Presentation: Stockholm(Sweden)
  • Year and Date: 2014-04-11 – 2014-04-15