Analysis of single nucleotide polymorphisms of glycosyltransferase gene responsible for the biosysnthesis of gastricο-glycans and its significance for genetic factor involved in the development of gastric diseases

• Project/Area Number: 21390104
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Shinshu University
• Principal Investigator: NAKAYAMA Jun 信州大学, 医学系研究科, 教授 (10221459)
• Co-Investigator(Kenkyū-buntansha): FUKUSHIMA Yoshimitsu 信州大学, 医学部, 教授 (70273084) ; AKAMATSU Taiji 信州大学, 医学部附属病院, 准教授 (80212413)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2011: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2010: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2009: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
• Keywords: 糖転移酵素 / 糖鎖遺伝子 / 一塩基遺伝子多型 / ピロリ菌 / 慢性胃炎 / ノックアウトマウス / 胃粘膜 / 慢性炎症 / 胃癌 / 1塩基遺伝子多型

Research Abstract

ο-glycans having terminalα1, 4-linked N-acetylglucosamine(αGlcNAc) are unique to the gastric gland mucous cell-type mucin, andα1, 4-N-acetylglucosaminyltranseferase(α4GnT) is the key enzyme responsible for the biosynthesis of the glycans. By analyzing the genome DNA prepared from the patients with H. pylori infected gastritis/gastric ulcer and gastric cancer, and the mutant mice deficient inαGlcNAc, we revealed that the single nucleotide polymorphism of A4GNT gene(rs22469459) could be an independent risk factor for gastric differentiated-type adenocarcinoma, and thatαGlcNAc prevents gastric cancer by suppressing tumor-promoting chronic inflammation, respectively

Research Products

• [Journal Article] Expression of long-form N-acetylglucosamine-6-0-sulfo-transferase1in human high endothelial venules (2012)
  • Author(s): Fujiwara M, KobayashiM, Hoshino H, Uchimura K, NakadaT, Masumoto J, Sakai Y, Fukuda M, Nakayama J
  • Journal Title: J Histochem Cytochem Volume: 60 Issue: 5 Pages: 397-407
  • DOI: 10.1369/0022155412437613
  • Peer Reviewed
• [Journal Article] Essential role of gastric gland mucin in preventing gastric cancer in mice (2012)
  • Author(s): Karasawa F, Shiota A, Goso Y, Kobayashi M, Sato Y, Masumoto J, Fujiwara M, Yokosawa S, Muraki T, Miyagawa S, Ueda M, Fukuda MN, Fukuda M, Ishihara K, Nakayama J
  • Journal Title: J Clin Invest Volume: 122 Issue: 3 Pages: 923-934
  • DOI: 10.1172/jci59087
  • Peer Reviewed
• [Journal Article] Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome (2012)
  • Author(s): Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, Ohta T, Niikawa N, Miyatake S, Okada I, Mizuguchi T, Doi H, Saitsu H, Miyake N, Matsumoto N
  • Journal Title: Nat Genet Volume: 44 Issue: 4 Pages: 376-378
  • DOI: 10.1038/ng.2219
  • Peer Reviewed
• [Journal Article] Targeted drug delivery to tumor vasculature by a carbohydrate mimetic peptide (2011)
  • Author(s): Hatakeyama S, Sugihara K, Shibata TK, Nakayama J, Akama TO, Tamura N, Wong S, Bobkov AA, Takano Y, Ohyama C, Fukuda M, Fukuda MN
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Issue: 49 Pages: 19587-19592
  • DOI: 10.1073/pnas.1105057108
  • Peer Reviewed
• [Journal Article] HNK-1 glycan functions as a tumor suppressor for astrocytic tumor (2011)
  • Author(s): Suzuki M, Suzuki M, Kobayashi T, Sato Y, Nakayama J, Suzuki A, Bao X, Angata K, Fukuda M
  • Journal Title: J Biol Chem Volume: 286 Issue: 37 Pages: 32824-32833
  • DOI: 10.1074/jbc.m111.245886
  • Peer Reviewed
• [Journal Article] An integrinα4β7・IgG heterodimeric chimera binds to MAdCAM-1 on high endothelial venules in gut-associated lymphoid tissue (2011)
  • Author(s): Hoshino H, Kobayashi M, Mitoma J, Sato Y, Fukuda M, Nakayama J
  • Journal Title: J Histochem Cytochem Volume: 59 Issue: 6 Pages: 572-583
  • DOI: 10.1369/0022155411404416
  • Peer Reviewed
• [Journal Article] O-Glycans carrying non-sulfated sialyl Lewis X appearing on HEV-like vessels in gastric MALT lymphoma function as L-selectin ligands (2011)
  • Author(s): Kobayashi M, Mitoma J, Hoshino H, Yu SY, Shimojo Y, Suzawa K, Khoo KH, Fukuda M, Nakayama J
  • Journal Title: J Pathol Volume: 224 Issue: 1 Pages: 67-77
  • DOI: 10.1002/path.2851
  • Peer Reviewed
• [Journal Article] Glycoside hydrolase family 89α-N-acetylglucosaminidase from Clostridium perfringens specifically acts on GlcNAcα1, 4Galβ1R at the non-reducing terminus of O-glycans in gastric mucin (2011)
  • Author(s): Fujita M, Tsuchida A, Hirata A, Kobayashi N, Goto K, Osumi K, Hirose Y, Nakayama J, Yamanoi T, Ashida H, Mizuno K
  • Journal Title: J Biol Chem Volume: 286 Issue: 8 Pages: 6479-6489
  • DOI: 10.1074/jbc.m110.206722
  • Peer Reviewed
• [Journal Article] Inflammasome activation of cardiac fibroblasts is effential for myocardial ischemia/reperfusion injury (2011)
  • Author(s): Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F, Morimoto H, Izawa A, Takahashi Y, Masumoto J, Koyama J, Hongo M, Noda T, Nakayama J, Sagara J, Taniguchi S, Ikeda U
  • Journal Title: Circulation Volume: 123 Issue: 6 Pages: 594-604
  • DOI: 10.1161/circulationaha.110.982777
  • Peer Reviewed
• [Journal Article] Reduced glycosylation ofα-dystroglycans on carcinoma cells contributes to formation of highly infiltrative histological patterns in prostate cancer (2011)
  • Author(s): Shimojo H, Kobayashi M, Kamigaito T, Shimojo Y, Fukuda M, Nakayama J
  • Journal Title: Prostate Volume: 71 Issue: 11 Pages: 1151-1157
  • DOI: 10.1002/pros.21330
  • Peer Reviewed
• [Journal Article] Membrane-associated activation of cholesterolα-glucosyltransferase, an enzyme responsible for biosynthesis of cholesteryl-α-D-glucopyranoside in Helicobacter pylori critical for its survival (2011)
  • Author(s): Hoshino H, Tsuchida A, Kametani K, Mori M, Nishizawa T, Suzuki T, Nakamura H, Lee H, Ito Y, Kobayashi M, Masumoto J, Fujita M, Fukuda M, Nakayama J
  • Journal Title: J Histochem Cytochem Volume: 59 Issue: 1 Pages: 98-105
  • DOI: 10.1369/jhc.2010.957092
  • Peer Reviewed
• [Journal Article] Delineation of dermatan 4-O-sulfotransferase 1 deficient Ehlers-Danlos syndrome : observation of two additional patients and comprehensive review of 20 reported patients (2011)
  • Author(s): Shimizu K, Okamoto N, Miyake N, Taira K, Sato Y, Matsuda K, Akimaru N, Ohashi H, Wakui K, Fukushima Y, Matsumoto N, Kosho T
  • Journal Title: Am J Med Genet A Volume: 155A Issue: 8 Pages: 949-1958
  • DOI: 10.1002/ajmg.a.34115
  • Peer Reviewed
• [Journal Article] Introduction of an examination and treatment for Helicobacter pylori infection in high school health screening (2011)
  • Author(s): Akamatsu T, Ichikawa S, Okudaira S, Yokosawa S, Iwaya Y, Suga T, Ota H, Tanaka E
  • Journal Title: J Gastroenterol Volume: 46 Issue: 12 Pages: 353-1360
  • DOI: 10.1007/s00535-011-0450-6
  • NAID: 10030295111
  • Peer Reviewed
• [Journal Article] Pmminent expression of sialyl Lewis X-capped core 2-branched O-glycans on high endothelial venule-like vessels in gastric MALT lymhoma (2011)
  • Author(s): 小林基弘, 他
  • Journal Title: journal of pathology Volume: 224 Pages: 67-77
  • Peer Reviewed
• [Journal Article] An integrin α4β7・IgG heterodimeric chimera binds to MAdCAM-1 on high endothelial venules in gut-associated lymphoid tissue (2011)
  • Author(s): 星野瞳, 他
  • Journal Title: Journal of Histochemistry and Cytochemistry Volume: 59(印刷中)
  • Peer Reviewed
• [Journal Article] Core2 O-glycan structure functions in gastrointestinal cell differentiation by regulating cell surface expression of sucrase isomaltase and dipeptidyl peptidase-IV (2010)
  • Author(s): Lee SH, Yu SY, Nakayama J, Khoo KH, Stone EL, Fukuda M, Marth JD, Fukuda M
  • Journal Title: Biol. Chem Volume: 285 Issue: 48 Pages: 37683-37692
  • DOI: 10.1074/jbc.m110.162735
  • Peer Reviewed
• [Journal Article] Usefulness of double balloon enteroscopy and video capsule endoscopy for the diagnosis and management of primary follicular lymphoma of the gastrointestinal tract in its early stages (2010)
  • Author(s): Akamatsu T, Kaneko Y, Ota H, Miyabayashi H, Arakura N, Tanaka E
  • Journal Title: Dig Endosc Volume: 22 Issue: 1 Pages: 33-38
  • DOI: 10.1111/j.1443-1661.2009.00915.x
  • NAID: 10028186428
  • Peer Reviewed
• [Journal Article] Non-thermal cytocidal effect of infrared irradiation on cultured cancer cells using specialized device (2010)
  • Author(s): Tanaka, et al.
  • Journal Title: Cancer Science (in press)
  • Peer Reviewed
• [Journal Article] Tumor suppressor function of lamining-bindingα-dystroglycan requires a distinctβ3-N-acetylglucosaminyltransferase (2009)
  • Author(s): Bao X, Kobayashi M, Hatakeyama S, Angata K, Gullberg D, Nakayama J, Fukuda MN, Fukuda M
  • Journal Title: Proc Natl Acad Sci USA Volume: 106 Issue: 29 Pages: 12109-12114
  • DOI: 10.1073/pnas.0904515106
  • Peer Reviewed
• [Journal Article] Interleukin-1βsuppression in Blau syndrome : comment on the article by Martin et al (2009)
  • Author(s): Masumoto J, Yamazaki T, Ohta K, Nakayama J, Agematsu K
  • Journal Title: Arthritis Rheum Volume: 60 Issue: 8 Pages: 2544-2545
  • DOI: 10.1002/art.24691
  • Peer Reviewed
• [Journal Article] Therapeutic and preventive effects of methotrexate on zymosan-induced arthritis in SKG mice (2009)
  • Author(s): Nagate T, Kawai J, Nakayama J
  • Journal Title: J Vet Med Sci Volume: 71 Pages: 713-717
  • URL: http://dx.doi.org/10.1292/jvms.71.713
  • Peer Reviewed
• [Journal Article] Identification of mRNA splicing factors as the endothelial receptor for carbohydrate-dependent lung colonization of cancer cells (2009)
  • Author(s): Hatakeyama S, Sugihara K, Nakayama J, Akama TO, Wong SM, Kawashima H, Zhang J, Smith DF, Ohyama C, Fukuda M, and Fukuda MN.
  • Journal Title: Proc. Natl. Acad. Sci Volume: 106 Issue: 9 Pages: 3095-3100
  • DOI: 10.1073/pnas.0810110106
  • Peer Reviewed
• [Journal Article] Role of ASC in the mouse model of Helicobacter pylori Infection (2009)
  • Author(s): Benoit BN, Kobayashi M, Kawakubo M, Takeoka M, Sano K, Zou J, Itano N, Tsutsui H, Noda T, Fukuda M, Nakayama J, Taniguchi S
  • Journal Title: J Histochem Cytochem Volume: 57 Issue: 4 Pages: 327-338
  • DOI: 10.1369/jhc.2008.952366
  • Peer Reviewed
• [Journal Article] GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitis (2009)
  • Author(s): Kobayashi M, Hoshino H, Masumoto J, Fukushima M, Suzawa K, Kageyama S, Suzuki M, Ohtani H, Fukuda M, Nakayama J
  • Journal Title: Inflamm Bowel Dis Volume: 15 Issue: 5 Pages: 679-706
  • DOI: 10.1002/ibd.20827
  • Peer Reviewed
• [Presentation] Dual roles of gastric gland mucin-specific O-glycan on prevention of gastric cancer (2011)
  • Author(s): Nakayama J
  • Organizer: The 21st Hiroshima Cancer Seminar-The 5th Three Universities' Consortium International Symposium" Recent Progress in Carcinogenesis, Progression and Management of Upper GI Cancers"
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 2011-11-06
• [Presentation] Dual roles of gastric gland mucin-specific O-glycan on prevention of gastric cancer (2011)
  • Author(s): 中山淳
  • Organizer: The 21st Hiroshima Cancer Seminar-The 5th Three Universities' Consortium International Symposium "Recent Progress in Carcinogenesis, Progression and Management of Upper GI Cancers"
  • Place of Presentation: 広島市(招待講演)
  • Year and Date: 2011-11-06
• [Presentation] Interaction of Helicobacter pylori and O-glycans in stomach (2011)
  • Author(s): Nakayama J
  • Organizer: Glycobiology Japan-Netherland Joint Seminar 2011
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2011-10-11
• [Presentation] Interaction of Helicobacter pylori and O-glycans in stomach (2011)
  • Author(s): 中山淳
  • Organizer: Glycobiology Japan-Nether land Joint Seminar 2011
  • Place of Presentation: 名古屋市(招待講演)
  • Year and Date: 2011-10-11
• [Presentation] 防御因子としての胃腺粘液糖鎖の役割 (2011)
  • Author(s): 中山淳
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 2011-04-29
• [Presentation] 防御因子としての胃腺粘液糖鎖の役割 (2011)
  • Author(s): 中山淳
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜市(招待講演)
  • Year and Date: 2011-04-29
• [Presentation] 胃腺粘液の機能-糖鎖研究からのアプローチ (2011)
  • Author(s): 中山淳
  • Organizer: 第29回Cytoprotection研究会
  • Place of Presentation: 京都市
  • Year and Date: 2011-03-11
• [Presentation] 糖鎖研究の新展開 (2010)
  • Author(s): 中山淳
  • Organizer: 第37回日本臓器保存生物医学会定期学術集会
  • Place of Presentation: 新潟市
  • Year and Date: 2010-11-20
• [Presentation] 糖鎖研究のすすめ (2009)
  • Author(s): 中山淳
  • Organizer: 第74回日本泌尿器科学会東部総会
  • Place of Presentation: 松本市
  • Year and Date: 2009-10-29
• [Book] 第3の生命鎖糖鎖の謎が今、解る(文部科学省特定領域研究踏査によるタンパク質と分子複合体の機能調節Functional Glycomics研究成果公開シンポジウム) (2009)
  • Author(s): 中山淳,古川鋼一
  • Publisher: ピロリ菌と戦う糖鎖
• [Remarks]
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/chair/i-2byori/index.html
• [Remarks]
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/chair/i-2byori/index.html
• [Patent(Industrial Property Rights)] 特許 (2010)
  • Inventor(s): 田中洋平, 他
  • Industrial Property Rights Holder: 信州大学, 他
  • Filing Date: 2010-02-05
  • Overseas