Analysis of the mechanism for liver cancer developing from non-alcoholic steatohepatitis by next-generation sequencing

• Project/Area Number: 23701082
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnosis
• Research Institution: Kyoto University
• Principal Investigator: KITAMOTO Takuya 京都大学, 医学(系)研究科(研究院), 特定技術職員 (10456882)
• Research Collaborator: HOTTA Kikuko 京都大学, 医学(系)研究科(研究院), 特定助教 (30360639) ; KITAMOTO Aya 京都大学, 医学(系)研究科(研究院), 教務補佐員 (30381627)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ゲノムワイド相関解析 / 非アルコール性脂肪肝炎 / 次世代シークエンサー / PNPLA3 / SAMM50 / PARVB / 次世代シークエンス / 異所性脂肪蓄積

Research Abstract

For GWAS, 372 Japanese NAFLD subjects and 934 control individuals were analyzed. For replication studies, 172 NAFLD and 1012 control subjects were monitored. Rs738409 in the PNPLA3 gene was most strongly associated with NAFLD. Rs2896019, and rs381062 in the PNPLA3 gene, rs738491, rs3761472, and rs2143571 in the SAMM50 gene, rs6006473, rs5764455, and rs6006611 in the PARVB gene had also significant and were associated with decreased serum triglycerides and increased AST and ALT in NAFLD patients. These SNPs were associated with steatosis grade and NAS. Rs738409, rs2896019, rs738491, rs6006473, rs5764455, and rs6006611 were associated with fibrosis. We amplified approximately 150kb region including PNPLA3 of 19 NAFLD and 9 control subjects and analyzed by next-generation sequencing.

Research Products

• [Journal Article] <i>NUDT3</i> rs206936 is associated with body mass index in obese Japanese women (2013)
  • Author(s): Kitamoto A, Kimoto T, Mizusawa S, Teranishi H, So R, Matsuo T, Nakata Y, Hyogo H, Ochi H, Nakamura T, Kamohara S, Miyatake N, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Masuzaki H, Ueno T, Chayama K, Hamaquchi K, Yamada K, Hanafusa T, Okikawa S, Sakata T, Tanaka K, Matsuzawa Y, Nako K, Sekine A, Hotta K
  • Journal Title: Endocrine Journal Volume: 60 Issue: 8 Pages: 991-1000
  • DOI: 10.1507/endocrj.EJ13-0100
  • NAID: 10031195769
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan (2013)
  • Author(s): Kitamoto T, Kitamoto A, Yoneda M, Hyogo H, Ochi H, Nakamura T, Teranishi H, Mizusawa S, Ueno T, Chayama K, Nakajima A, Nakao K, Sekine A, Hotta K.
  • Journal Title: Hum Genet Volume: (印刷中)
  • NAID: 120005474457
  • Peer Reviewed
• [Journal Article] Replication Study of 15 Recently Published Loci for Body Fat Distribution in the Japanese Population (2013)
  • Author(s): Hotta K
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 20 Issue: 4 Pages: 336-350
  • DOI: 10.5551/jat.14589
  • NAID: 130004444671
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan. (2013)
  • Author(s): Kitamoto T
  • Journal Title: Human Genetics Volume: 3 Issue: 7 Pages: 1-10
  • DOI: 10.1007/s00439-013-1294-3
  • NAID: 120005474457
  • Peer Reviewed
• [Journal Article] Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography (2012)
  • Author(s): Hotta K, et al (last)
  • Journal Title: J Hum Genet Volume: (In press) Issue: 5 Pages: 305-310
  • DOI: 10.1038/jhg.2012.21
  • Peer Reviewed
• [Journal Article] Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women (2012)
  • Author(s): Hotta K, et al (last)
  • Journal Title: J Hum Genet Volume: 57 Issue: 1 Pages: 46-51
  • DOI: 10.1038/jhg.2011.127
  • Peer Reviewed
• [Journal Article] Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area (2011)
  • Author(s): Hotta K, et al (last)
  • Journal Title: J Hum Genet Volume: 56 Issue: 10 Pages: 716-719
  • DOI: 10.1038/jhg.2011.86
  • Peer Reviewed
• [Journal Article] Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population (2011)
  • Author(s): Hotta K, et al (last)
  • Journal Title: J Hum Genet Volume: 56 Issue: 9 Pages: 716-719
  • DOI: 10.1038/jhg.2011.74
  • Peer Reviewed
• [Presentation] 次世代シーケンサーを用いた薬物代謝関連遺伝子群のターゲットリシーケンス (2012)
  • Author(s): 北本綾
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 東京都京王プラザホテル
  • Year and Date: 2012-10-25
• [Presentation] 次世代シーケンサーを用いた薬物代謝関連遺伝子群のターゲットリシーケンス (2012)
  • Author(s): 北本綾
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 東京都 京王プラザホテル
• [Presentation] 薬物代謝関連遺伝子群の高密度、高精度な遺伝子型決定法の確立 (2011)
  • Author(s): 北本綾
  • Organizer: 日本人類遺伝学会第56回大会
  • Place of Presentation: 千葉県幕張メッセ
  • Year and Date: 2011-11-11
• [Presentation] PNPLA3遺伝子上のrs738409と非アルコール性脂肪肝炎とのケース・コントロール相関解析 (2011)
  • Author(s): 堀田紀久子、北本卓也、北本綾、米田正人、中島淳、上野登隆、兵庫秀幸、越智秀典、茶山一彰、関根章博、中尾一和
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 北海道 さっぽろ芸術文化の館
• [Presentation] 薬物代謝関連遺伝子群の高密度、高精度な遺伝子型決定法の確立 (2011)
  • Author(s): 北本綾、北本卓也、水澤精穂、寺西啓、堀田紀久子、上嶋健治、小杉眞司、中尾一和、関根章博
  • Organizer: 日本人類遺伝学会第56回大会
  • Place of Presentation: 千葉県 幕張メッセ