Evidence of gene-environment interaction for the RUNX2 gene and environmental tobacco smoke in controlling the risk of cleft lip with/without cleft palate

Tao Wu, M. Daniele Fallin, Min Shi, Ingo Ruczinski, Kung Yee Liang, Jacqueline B. Hetmanski, Hong Wang, Roxann G. Ingersoll, Shangzhi Huang, Xiaoqian Ye, Yah Huei Wu-Chou, Philip K. Chen, Ethylin Wang Jabs, Bing Shi, Richard Redett, Alan F. Scott, Jeffrey C. Murray, Mary L. Marazita, Ronald G. Munger, Terri H. Beaty

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16 Citations (Scopus)

Abstract

This study examined the association between 49 markers in the Runt-related transcription factor 2 (RUNX2) gene and nonsyndromic cleft lip with/without cleft palate (CL/P) among 326 Chinese case-parent trios, while considering gene-environment (GxE) interaction and parent-of-origin effects. Five single-nucleotide polymorphisms (SNPs) showed significant evidence of linkage and association with CL/P and these results were replicated in an independent European sample of 825 case-parent trios. We also report compelling evidence for interaction between markers in RUNX2 and environmental tobacco smoke (ETS). Although most marginal SNP effects (i.e., ignoring maternal exposures) were not statistically significant, eight SNPs were significant when considering possible interaction with ETS when testing for gene (G) and GxE interaction simultaneously or when considering GxE alone. Independent samples from European populations showed consistent evidence of significant GxETS interaction at two SNPs (rs6904353 and rs7748231). Our results suggest genetic variation in RUNX2 may influence susceptibility to CL/P through interacting with ETS.

Original languageEnglish
Pages (from-to)76-83
Number of pages8
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume94
Issue number2
DOIs
Publication statusPublished - Feb 1 2012
Externally publishedYes

Keywords

  • Gene-environment interaction
  • Imprinting
  • Oral clefts
  • Parent-of-origin effects
  • RUNX2

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Developmental Biology

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    Wu, T., Fallin, M. D., Shi, M., Ruczinski, I., Liang, K. Y., Hetmanski, J. B., Wang, H., Ingersoll, R. G., Huang, S., Ye, X., Wu-Chou, Y. H., Chen, P. K., Jabs, E. W., Shi, B., Redett, R., Scott, A. F., Murray, J. C., Marazita, M. L., Munger, R. G., & Beaty, T. H. (2012). Evidence of gene-environment interaction for the RUNX2 gene and environmental tobacco smoke in controlling the risk of cleft lip with/without cleft palate. Birth Defects Research Part A - Clinical and Molecular Teratology, 94(2), 76-83. https://doi.org/10.1002/bdra.22885