Development of next-generation anticoagulant therapy using nutri-pharmaogenomic approach

• Project/Area Number: 25460661
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kanazawa Medical University
• Principal Investigator: KAJINAMI Kouji 金沢医科大学, 医学部, 教授 (40262563)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ファーマコゲノミクス / 血栓 / 抗凝固薬 / 脂質代謝 / ビタミンK / ファーマコゲノミックス

Outline of Final Research Achievements

Intestinal cholesterol transporter NPC1L1-genotype dependent influence of dietary vit K intake on warfarin anticoagulation was examined in 232 patients. Only in those with VKORC1 -1639A/G heterozygotes, NPC1L1 functional SNP rs2072813 influenced significantly on the relation between warfarin efficiency and the amount of vit K intake, suggesting possible role of NPC1L1 linking lipid metabolism and thrombogenic diseases.
In subjects receiving novel anticoagulant, Xa inhibitor, Xa activity and several biomarkers were measured in 50 patients. F1+2 showed the best association with Xa activity among examined variables, and Xa activity in addition to sex, age, body weight, and creatinine was independent determinant for F1+2 level.

Research Products

• [Journal Article] Circulating glutamate and taurine levels are associated with the generation of reactive oxygen species in paroxysmal atrial fibrillation. (2016)
  • Author(s): Takano S, Fujibayashi K, Fujioka N, Ueno E, Wakasa M, Kawai Y, Kajinami K.
  • Journal Title: Disease Markers Volume: 2016 Pages: 7650976-7650976
  • DOI: 10.1155/2016/7650976
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lipoprotein(a): Revisiting a Next Therapeutic Target (2016)
  • Author(s): Kajinami K
  • Journal Title: Circulation Journal Volume: 80 Issue: 2 Pages: 329-331
  • DOI: 10.1253/circj.CJ-15-1381
  • NAID: 130005120889
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical characteristics of patients with Rutherford category IV, compared with V and VI. (2015)
  • Author(s): Tsuchiya T, Iida O, Shiraki T, Soga Y, Hirano K, Suzuki K, Yamaoka T, Miyashita Y, Kitayama M, Kajinami K.
  • Journal Title: SAGE Open Med. Volume: 3 Pages: 7087-7087
  • DOI: 10.1177/2050312115597087
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nutri-pharmacogenomics of warfarin anticoagulation therapy: VKORC1 genotype-dependent influence of dietary vitamin K intake. (2014)
  • Author(s): Saito R, Takeda K, Yamamoto K, Nakagawa A, Aoki H, Fujibayashi K, Wakasa M, Motoyama A, Iwadare M, Ishida R, Fujioka N, Tsuchiya T, Akao H, Kawai Y, Kitayama M, Kajinami K.
  • Journal Title: J Thromb Thrombolysis. Volume: 38 Issue: 1 Pages: 105-114
  • DOI: 10.1007/s11239-013-0978-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increased levels of the oxidative stress marker, nitrotyrosine in patients with provocation test-induced coronary vasospasm. (2014)
  • Author(s): Tanabe K, Kawai Y, Kitayama M, Akao H, Ishida R, Motoyama A, Wakasa M, Saito R, Aoki H, Fujibayashi K, Watanabe M, Tsuchiya T, Kimura H, Yoshida K, Kajinami K.
  • Journal Title: Journal of Cardiology Volume: 印刷中 Issue: 2 Pages: 86-90
  • DOI: 10.1016/j.jjcc.2013.11.017
  • Peer Reviewed
• [Journal Article] ABCA1 gene variation and heart disease risk reduction in the elderly during pravastatin treatment (2014)
  • Author(s): Akao H, Polisecki1 E, Schaefer EJ, Trompet S, Robertson M, Ford I, Jukema JW, de Craen AJM, Packard C, Buckley BM, Kajinami K.
  • Journal Title: Atherosclerosis Volume: 235 Issue: 1 Pages: 176-181
  • DOI: 10.1016/j.atherosclerosis.2014.04.030
  • Peer Reviewed
• [Journal Article] ABCA1 gene variation and heart disease risk reduction in the elderly during pravastatin treatment. (2014)
  • Author(s): Akao H, Polisecki1 E, Schaefer EJ, Trompet S, Robertson M, Ford I, Jukema JW, de Craen AJM, Packard C, Buckley BM, Kajinami K.
  • Journal Title: Atherosclerosis Volume: -
  • Peer Reviewed
• [Journal Article] Myocardial sympathetic innervation, function, and oxidative metabolism in non-infarcted myocardium in patients with prior myocardial infarction (2013)
  • Author(s): Aoki H, Matsunari I, Nomura Y, Fujita W, Komatsu R, Miyazaki Y, Nekolla SG, Kajinami K.
  • Journal Title: Ann Nucl Med. Volume: 27 Pages: 523-531
  • NAID: 10031189355
  • Peer Reviewed
• [Journal Article] Management and two-year long-term clinical outcome of acute coronary syndrome in Japan: prevention of atherothrombotic incidents following ischemic coronary attack (PACIFIC) registry. (2013)
  • Author(s): Daida H, Miyauchi K, Ogawa H, Yokoi H, Matsumoto M, Kitakaze M, Kimura T, Matsubara T, Ikari Y, Kimura K, Tsukahara K, Origasa H, Morino Y, Tsutsui H, Kobayashi M, Isshiki T; PACIFIC investigators.
  • Journal Title: Circ J. Volume: 77 Pages: 934-943
  • Peer Reviewed
• [Presentation] Prothrombin activation fragment (F1+2) as an index of anticoagulant therapy with factor Xa inhibitor in atrial fibrillation (2016)
  • Author(s): Ueno E, Fujibayashi K, Sawaguchi J, Yasuda Y, Takano S, Saito R, Wakasa M, Fujioka N, Kawai Y, Kajinami K.
  • Organizer: ESC congress 2016
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Nutri-pharmacogenomic interaction of intestinal cholesterol transporter (NPC1L1) with VKORC1 as a determinant of warfarin anticoagulation (2016)
  • Author(s): Saito R, Takeda K, Aoki H, Fujibayashi K, Wakasa M, Motoyama A, Fujioka N, Akao H, Kawai Y, Tsuchiya T, Kitayama M, Kajinami K.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台国際会議場（宮城県仙台市）
  • Year and Date: 2016-03-18