Recent genetics of Cleft Lip and Palate

• Project/Area Number: 20791560
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Aichi Gakuin University
• Principal Investigator: SUZUKI Satoshi Aichi Gakuin University, 歯学部, 非常勤助教 (30468996)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 口唇裂 / 口蓋裂 / 口唇口蓋裂 / TGFB遺伝子 / BMP4遺伝子

Research Abstract

Nonsyndromic cleft lip with or without cleft palate (CL/P), a common birth defect, is a complex trait, arising from the influence of genetic and environmental factors. There are many studies have been reported. Our study supports the role of BMP4 in nonsyndromic CL/P, with mutations in BMP4 associated with microforms and OO, and polymorphic variants increasing the susceptibility to overt CL/P.A recent study of variants in the IRF6 gene showed variants in an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. We have also previously reported the linkage of NS CL/P to the 6p23 region that contains TFAP2A gene. We genotyped 8 SNPs in and near TFAP2A and FBAT was used for transmission disequilibrium test. A statistically significant association between CL/P and TFAP2A (p<0.001) was shown for rs1675414. These results support a direct role for variation of TFAP2A in orofacial clefting and suggests that examination of additional members of this pathway and deeper investigation of SNPs at the TFAP2A locus may disclose etiologic variants. Also recent Genome wide associations study discovered multiple loci such as MAFB, VAX1 and PAX7. We genotyped single nucleotide polymorphisms (SNPs) in or near VAX1, MAFB and PAX7. Results showed strong association between these genes and cleft lip and palate.

Research Products

• [Journal Article] Mutations inBMP4 Are Associated with Subepithelial, Microform, and Overt Cleft Lip (2009)
  • Author(s): Suzuki S, Marazita ML, Cooper ME, Miwa N, Hing A, Jugessur A, Natsume N, Shimozato K, Ohbayashi N, Suzuki Y, Niimi T, Minami K, Yamamoto M, Altannamar TJ, Erkhembaatar T, Furukawa H, Daack-Hirsch S, L' heureux J, Brandon CA, Weinberg SM, Nei swanger K, Deleyiannis FW, de Salamanca JE, Vieira AR, Lidral AC, Martin JF, Murray JC.
  • Journal Title: The American Journal of Human Genetics 84(3) Pages: 406-411
  • Peer Reviewed
• [Journal Article] Mutations inBMP4 Are Associated with Subepithelial, Microform, and Overt Cleft Lip (2009)
  • Author(s): 鈴木聡
  • Journal Title: The American Journal of Human Genetics (in press)
  • Peer Reviewed
• [Presentation] Replication of genome wide association findings for Cleft Lip and Palate a role for variants in MAFB, VAX1 and PAX7 in Asian population (2010)
  • Author(s): Satoshi Suzuki
  • Organizer: アメリカ人類遺伝学会総会
  • Place of Presentation: ウォルターE.ワシントンコンベンションセンター(米国ワシントンDC)
• [Presentation] Replication of genome wide association findings for Cleft Lip and Palste a role for variants in MAFB, VAX1 and PAX7 in Asian population (2010)
  • Author(s): 鈴木聡
  • Organizer: アメリカ人類遺伝学会総会
  • Place of Presentation: ウォルターE.ワシントンコンベンションセンター(米国ワシントンDC)
• [Presentation] TFAP2A is associated with nonsyndromic Cleft Lip and Palate (2009)
  • Author(s): Satoshi Suzuki
  • Organizer: american sociaty of human genetics
  • Place of Presentation: Hawaii waikiki
• [Presentation] TFAP2A is associated with nonsyndromic Cleft Lip and Palate (2009)
  • Author(s): 鈴木聡
  • Organizer: american sociaty of human genetics
  • Place of Presentation: Hawaii, waikiki