Candidate gene study of cleft lip and/or cleft palate in Japan and Vietnam by international collaboration.

• Project/Area Number: 26861757
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Aichi Gakuin University
• Principal Investigator: SUZUKI SATOSHI 愛知学院大学, 歯学部, 非常勤助教 (30468996)
• Research Collaborator: NATSUME NAGATO 愛知学院大学, 歯学部, 教授 (90183532) ; YOSHIURA Koh-ichiro 長崎大学, 原爆後障害医療研究所, 教授 (00304931)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 口唇口蓋裂 / 遺伝学 / 遺伝子 / DNA / TDT

Outline of Final Research Achievements

Genome wide association studies of non-syndromic cleft lip and/or cleft palate have been identified multiple genetic loci including MAFB, VAX1, PAX7, FOXE1 and ABCA4. We used independent 404 case-parents trios from Vietnam which were cleft lip only (CLO;104 trios), cleft lip and palate (CLP;135 trios) and cleft palate only (CPO;165 trios) were genotyped by either TaqMan assays or Fluidigm. Transmission disequilibrium test was performed by Family based Association Test and PLINK. Statistically significant associations were observed in genes incluging IRF6, FOXE1 and MAFB. Regarding CL/P, There were associations with IRF6 (rs2235371, p= 6.80E-06 and rs2013162 p= 0.03486) and MAFB (rs17820943, p= 0.002266, rs13041247 and rs11696257, p= 0.001862). Also FOXE1 (rs894673 and rs3758249, p= 0.02) was slightly associated with CL/P. However, after Bonferroni correction, only IRF6 showed significant association. In Japanese, only VAX1 showed statistical significance (rs7078160, p=0.00511)

Research Products

• [Journal Article] Jacobsen syndrome associated with cleft lip:Apatient report and review (2015)
  • Author(s): Tomoki Kato, Seiji Mizuno, Kenji Kurosawa, Satoshi Suzuki, Teruyuki Niimi, Nagato Natsume
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 27(2) Issue: 2 Pages: 236-238
  • DOI: 10.1016/j.ajoms.2014.01.002
  • Peer Reviewed / Open Access
• [Journal Article] Repliction of 13q31.1 Association in Nonsyndromic Cleft lip with Cleft Palate in Europeans (2015)
  • Author(s): Zhonglin Jia, Elizabeth J. Leslie, Margaret E. Cooper, Azeez Butali, Jennifer Standley, Jennifer Rigdon, Satoshi Suzuki, Ayana Gongorjav, T.Enkhtur Shonkhuuz, Nagato Natsume, Bing Shi, Mry L. Marazita, Jeffrey C. Murray
  • Journal Title: American Journal of Medical Genetics Volume: 167(5) Issue: 5 Pages: 1054-60
  • DOI: 10.1002/ajmg.a.36912
  • Peer Reviewed / Open Access
• [Presentation] The mechanism of cleft palate after palatal fusion (2015)
  • Author(s): S. Suziki, H.Imura, N.Natsume,
  • Organizer: 65th American Society of Human Genetics Annual Meeting
  • Place of Presentation: Baltimore（USA）
  • Year and Date: 2015-10-06
  • Int'l Joint Research