Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations

Ji Wan Park, Iain McIntosh, Jacqueline B. Hetmanski, Ethylin Wang Jabs, Craig A. Vander Kolk, Yah Huei Wu-Chou, Philip K. Chen, Samuel S. Chong, Vincent Yeow, Sun Ha Jee, Beyoung Yun Park, M. Daniele Fallin, Roxann Ingersoll, Alan F. Scott, Terri H. Beaty

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)


PURPOSE: The interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome has been shown to be associated with nonsyndromic cleft lip with or without palate in several populations. This study aimed to confirm the contribution of IRF6 to cleft lip with or without palate risk in additional Asian populations. METHODS: A set of 13 single nucleotide polymorphisms was tested for association with cleft lip with or without palate in 77 European American, 146 Taiwanese, 34 Singaporean, and 40 Korean case-parent trios using both the transmission disequilibrium test and conditional logistic regression models. RESULTS: Evidence of linkage and association was observed among all four populations; and two specific haplotypes [GC composed of rs2235373-rs2235371 (p.V274I) and AAG of rs599021-rs2235373-rs595918] showed the most significant over- and undertransmission among Taiwanese cases (P = 9 × 10 and P = 5 × 10, respectively). The AGC/CGC diplotype composed of rs599021-rs2235373-rs2013162 showed almost a 7-fold increase in risk among the Taiwanese sample (P < 10). These results confirmed the contribution of this gene to susceptibility of oral clefts across different populations; however, the specific single nucleotide polymorphisms showing statistical significance differed among ethnic groups. CONCLUSION: The high-risk genotypes and diplotypes identified here may provide a better understanding of the etiological role of this gene in oral clefts and potential options for genetic counseling.

Original languageEnglish
Pages (from-to)219-227
Number of pages9
JournalGenetics in Medicine
Issue number4
Publication statusPublished - Apr 1 2007
Externally publishedYes


  • Association
  • Ethnicity
  • Interferon regulatory factor 6
  • Oral cleft
  • Risk estimation
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics(clinical)


Dive into the research topics of 'Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations'. Together they form a unique fingerprint.

Cite this