Fetal polymorphisms at the ABCB1-transporter gene locus are associated with susceptibility to non-syndromic oral cleft malformations

Ardeshir Omoumi, Zihua Wang, Vincent Yeow, Yah Huei Wu-Chou, Philip K. Chen, Ingo Ruczinski, Joanne Cheng, Felicia S H Cheah, Caroline G. Lee, Terri H. Beaty, Samuel S. Chong

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


ATP-binding cassette (ABC) proteins in the placenta regulate fetal exposure to xenobiotics. We hypothesized that functional polymorphisms in ABC genes influence risk for non-syndromic oral clefts (NSOC). Both family-based and case-control studies were undertaken to evaluate the association of nine potentially functional single-nucleotide polymorphisms within four ABC genes with risk of NSOC. Peripheral blood DNA from a total of 150 NSOC case-parent trios from Singapore and Taiwan were genotyped, as was cord blood DNA from 189 normal Chinese neonates used as controls. In trios, significant association was observed between the ABCB1 single-nucleotide polymorphisms and NSOC (P<0.05). Only ABCB1 rs1128503 retained significant association after Bonferroni correction (odds ratio (OR)=2.04; 95% confidence interval (CI)=1.42-2.98), while rs2032582 and rs1045642 showed nominal significance. Association with rs1128503 was replicated in a case-control analysis comparing NSOC probands with controls (OR=1.58; 95% CI=1.12-2.23). A comparison between the mothers of probands and controls showed no evidence of association, suggesting NSOC risk is determined by fetal and not maternal ABCB1 genotype. The two studies produced a combined OR of 1.79 (95% CI=1.38-2.30). The T-allele at rs1128503 was associated with higher risk. This study thus provides evidence that potentially functional polymorphisms in fetal ABCB1 modulate risk for NSOC, presumably through suboptimal exclusion of xenobiotics at the fetal-maternal interface.

Original languageEnglish
Pages (from-to)1436-1441
Number of pages6
JournalEuropean Journal of Human Genetics
Issue number12
Publication statusPublished - Dec 1 2013
Externally publishedYes


  • ATP-binding cassette transporters
  • cleft lip
  • cleft palate
  • disease susceptibility
  • placenta
  • single-nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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