Comprehensive genetic analysis for the patients with familial hypercholesterolemia

• Project/Area Number: 26893094
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Cardiovascular medicine
• Research Institution: Kanazawa University
• Principal Investigator: TADA HAYATO 金沢大学, 大学病院, 助教 (90623653)
• Research Collaborator: Kathiresan Sekar 米国マサチューセッツ総合病院, ヒトゲノム研究所, 部長
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 家族性高コレステロール血症 / エクソーム解析 / exome / 網羅的遺伝子解析

Outline of Final Research Achievements

We identified a pathogenic mutation in LDL receptor gene, but could not lead to the identification of any novel genes. We conducted an international collaboration, collecting similar cases, leading to conclude that success rate of genetic analysis was ~20%. In addition, we identified a family with de novo mutation in LDL receptor gene, which, was the novel findings at least in the cases with familial hypercholesterolemia in an exome-wide manner.

Research Products

• [Journal Article] A de novo mutation of the LDL receptor gene as the cause of familial hypercholesterolemia identified using whole exome sequencing. (2016)
  • Author(s): Tada H, Hosomichi K, Okada H, Kawashiri MA, Nohara A, Inazu A, Tomizawa S, Tajima A, Mabuchi H, Hayashi K.
  • Journal Title: Clin Chim Acta. Volume: 453 Pages: 194-196
  • DOI: 10.1016/j.cca.2015.12.028
  • Peer Reviewed / Open Access
• [Journal Article] Exome sequencing in suspected monogenic dyslipidemias. (2015)
  • Author(s): Stitziel NO, Peloso GM, Abifadel M, Cefalu AB, Fouchier S, Motazacker MM, Tada H, Larach DB, Awan Z, Haller JF, Pullinger CR, Varret M, Noto D, Tarugi P, Kawashiri MA, Nohara A, Yamagishi M, Kathiresan S. et al.
  • Journal Title: Circ Cardiovasc Genet. Volume: 8 Issue: 2 Pages: 343-50
  • DOI: 10.1161/circgenetics.114.000776
  • Peer Reviewed / Open Access
• [Journal Article] Assessment of Coronary Atherosclerosis in Patients With Familial Hypercholesterolemia by Coronary Computed Tomography Angiography (2015)
  • Author(s): Tada H, Kawashiri MA, Okada H, Teramoto R, Konno T, Yoshimuta T, Sakata K, Nohara A, Inazu A, Kobayashi J, Mabuchi H, Yamagishi M, Hayashi K.
  • Journal Title: Am J Cardiol. Volume: 115 Issue: 6 Pages: 724-729
  • DOI: 10.1016/j.amjcard.2014.12.034
  • Peer Reviewed / Open Access
• [Journal Article] Lipoprotein metabolism in familial hypercholesterolemia: Serial assessment using a one- step ultracentrifugation method (2015)
  • Author(s): Hayato Tada, Masa-aki Kawashiri, Atsushi Nohara, Akihiro Inazu, Hiroshi Mabuchi, Masakazu Yamagishi, Kenshi Hayashi
  • Journal Title: Practical Laboratory Medicine Volume: 1 Pages: 22-27
  • DOI: 10.1016/j.plabm.2015.03.001
  • Peer Reviewed / Open Access
• [Presentation] A rare coincidence of sitosterolemia and familial Mediterranean fever identified by whole exome sequencing (2016)
  • Author(s): Hayato Tada
  • Organizer: 第80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
• [Presentation] A rare coincidence of sitosterolemia and familial Mediterranean fever identified by whole exome sequencing (2015)
  • Author(s): Hayato Tada
  • Organizer: American Heart Association 2015 Scientific Sessions
  • Place of Presentation: Orlando FL, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Whole Exome Sequencing in 23 Families with Familial Hypobetalipoproteinemia (2015)
  • Author(s): 多田 隼人
  • Organizer: 第60回日本人類遺伝学会
  • Place of Presentation: 京王プラザホテル （東京都新宿区）
  • Year and Date: 2015-10-14
• [Presentation] Coronary Plaque Burden Assessed with Coronary Computed Tomography Angiography Predicts Future Coronary Events in patients with Familial Hypercholesterolemia (2015)
  • Author(s): Hayato Tada
  • Organizer: 第79日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場 （大阪府大阪市）
  • Year and Date: 2015-04-24
• [Presentation] Abnormal Lipoprotein Metabolism Other than LDL Fraction in Familial Hypercholesterolemia:Serial analysis using Ultracentrifugation Method (2014)
  • Author(s): Tada H, Kawashiri MA, Nohara A, Inazu A, Yamagishi M
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Coronary Plaque Burden Assessed with Coronary Computed Tomography Angiography Predicts Future Coronary Events in patients with Familial Hypercholesterolemia (2014)
  • Author(s): Tada H, Kawashiri MA, Nakanishi C, Hodatsu A, Konno T, Yoshimuta T, Sakata K, Yoshimuta T, Hayashi K, Nohara A, Inazu A, Mabuchi H, Yamagishi M
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2014-11-15 – 2014-11-19