TGFA and IRF6 contribute to the risk of nonsyndromic cleft lip with or without cleft palate in northeast China

PLoS One. 2013 Aug 6;8(8):e70754. doi: 10.1371/journal.pone.0070754. Print 2013.

Abstract

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) are common birth defects with a complex etiology. Multiple interacting loci and possible environmental factors influence the risk of NSCL/P. 12 single nucleotide polymorphisms (SNPs) in 7 candidate genes were tested using an allele-specific primer extension for case-control and case-parent analyses in northeast China in 236 unrelated patients, 185 mothers and 154 fathers, including 128 complete trios, and 400 control individuals. TGFA and IRF6 genes showed a significant association with NSCL/P. In IRF6, statistical evidence of an association between rs2235371 (p = 0.003), rs2013162 (p<0.0001) and NSCL/P was observed in case-control analyses. Family based association tests (FBATs) showed over-transmission of the C allele at the rs2235371 polymorphism (p = 0.007). In TGFA, associations between rs3771494, rs3771523 (G3822A), rs11466285 (T3851C) and NSCL/P were observed in case-control and FBAT analyses. Associations between other genes (BCL3, TGFB3, MTHFR, PVRL1 and SUMO1) and NSCL/P were not detected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Child
  • China / epidemiology
  • Cleft Lip / epidemiology
  • Cleft Lip / genetics*
  • Cleft Palate / epidemiology
  • Cleft Palate / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Interferon Regulatory Factors / genetics*
  • Male
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Transforming Growth Factor alpha / genetics*

Substances

  • IRF6 protein, human
  • Interferon Regulatory Factors
  • Transforming Growth Factor alpha

Grants and funding

The funders of Scientific and Technological Project of Liaoning Province (Grant No.2009225007-7) played an important role in study design, data analysis, preparation of the manuscript and decision to publish, the Natural Science Foundation of Liaoning Province (Grant No. 2011010192-401) played an important role in the sample collection and diagnosis of the NSCL/P.