Human Genetics

, Volume 128, Issue 4, pp 401–410

Evidence of gene–environment interaction for the IRF6 gene and maternal multivitamin supplementation in controlling the risk of cleft lip with/without cleft palate

  • Tao Wu
  • Kung Yee Liang
  • Jacqueline B. Hetmanski
  • Ingo Ruczinski
  • Margaret Daniele Fallin
  • Roxann G. Ingersoll
  • Hong Wang
  • Shangzhi Huang
  • Xiaoqian Ye
  • Yah-Huei Wu-Chou
  • Philip K. Chen
  • Ethylin W. Jabs
  • Bing Shi
  • Richard Redett
  • Alan F. Scott
  • Terri H. Beaty
Original Investigation

DOI: 10.1007/s00439-010-0863-y

Cite this article as:
Wu, T., Liang, K.Y., Hetmanski, J.B. et al. Hum Genet (2010) 128: 401. doi:10.1007/s00439-010-0863-y

Abstract

Although multiple genes have been identified as genetic risk factors for isolated, non-syndromic cleft lip with/without cleft palate (CL/P), a complex and heterogeneous birth defect, interferon regulatory factor 6 gene (IRF6) is one of the best documented genetic risk factors. In this study, we tested for association between markers in IRF6 and CL/P in 326 Chinese case–parent trios, considering gene–environment interaction for two common maternal exposures, and parent-of-origin effects. CL/P case–parent trios from three sites in mainland China and Taiwan were genotyped for 22 single nucleotide polymorphisms (SNPs) in IRF6. The transmission disequilibrium test was used to test for marginal effects of individual SNPs. We used PBAT to screen the SNPs and haplotypes for gene–environment (G × E) interaction and conditional logistic regression models to quantify effect sizes for SNP–environment interaction. After Bonferroni correction, 14 SNPs showed statistically significant association with CL/P. Evidence of G × E interaction was found for both maternal exposures, multivitamin supplementation and environmental tobacco smoke (ETS). Two SNPs showed evidence of interaction with multivitamin supplementation in conditional logistic regression models (rs2076153 nominal P = 0.019, rs17015218 nominal P = 0.012). In addition, rs1044516 yielded evidence for interaction with maternal ETS (nominal P = 0.041). Haplotype analysis using PBAT also suggested interaction between SNPs in IRF6 and both multivitamin supplementation and ETS. However, no evidence for maternal genotypic effects or significant parent-of-origin effects was seen in these data. These results suggest IRF6 gene may influence risk of CL/P through interaction with multivitamin supplementation and ETS in the Chinese population.

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Tao Wu
    • 1
    • 2
  • Kung Yee Liang
    • 1
  • Jacqueline B. Hetmanski
    • 1
  • Ingo Ruczinski
    • 1
  • Margaret Daniele Fallin
    • 1
  • Roxann G. Ingersoll
    • 1
    • 3
  • Hong Wang
    • 2
  • Shangzhi Huang
    • 4
  • Xiaoqian Ye
    • 5
    • 6
  • Yah-Huei Wu-Chou
    • 7
  • Philip K. Chen
    • 7
  • Ethylin W. Jabs
    • 3
    • 5
  • Bing Shi
    • 8
  • Richard Redett
    • 3
  • Alan F. Scott
    • 3
  • Terri H. Beaty
    • 1
    • 9
  1. 1.Johns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  2. 2.Beijing University School of Public HealthBeijingChina
  3. 3.Johns Hopkins School of MedicineBaltimoreUSA
  4. 4.Peking Union Medical CollegeBeijingChina
  5. 5.Mount Sinai School of MedicineNew YorkUSA
  6. 6.Key Laboratory for Oral Biomedical Engineering of Ministry of Education, Hospital and School of StomatologyWuhan UniversityWuhanChina
  7. 7.Chang Gung Memorial HospitalTaoyuanTaiwan
  8. 8.West China College of StomatologySichuan UniversitySichuanChina
  9. 9.Department of Epidemiology, School of Public HealthJohns Hopkins UniversityBaltimoreUSA

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