Genetic variants in BRIP1 (BACH1) contribute to risk of nonsyndromic cleft lip with or without cleft palate

Birth Defects Res A Clin Mol Teratol. 2014 Sep;100(9):670-8. doi: 10.1002/bdra.23275. Epub 2014 Jul 21.


Background: The etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) is very complex and still not well elucidated. Given the critical role of DNA damage repair in the embryonic development, we decided to test the hypothesis that polymorphisms of selected DNA repair genes might contribute to the risk of NSCL/P in the Polish population.

Methods: Analysis of 36 polymorphisms in 12 DNA damage repair genes (ATM, BLM, BRCA1, BRIP1, E2F1, MLH1, MRE11A, MSH2, MSH6, NBN, RAD50, and RAD51) was conducted using TaqMan assays in a group of 263 NSCL/P patients and matched control group (n = 526).

Results: Statistical analysis of genotyping results revealed that nucleotide variants in the BRIP1 (BACH1) gene were associated with the risk of NSCL/P. Under assumption of a dominant model, the calculated odds ratios (ORs) for BRIP1 rs8075370 and rs9897121 were 1.689 (95% confidence interval [CI], 1.249-2.282; p = 0.0006) and 1.621 (95% CI, 1.200-2.191; p = 0.0016), respectively. These results were statistically significant even after applying multiple testing correction. Additional evidence for a causative role of BRIP1 in NSCL/P etiology was provided by haplotype analysis. Borderline association with a decreased risk of this anomaly was also observed for BLM rs401549 (ORrecessive = 0.406; 95% CI, 0.223-1.739; p = 0.002) and E2F1 rs2071054 (ORdominant = 0.632; 95% CI, 0.469-0.852; p = 0.003).

Conclusion: Our study suggests that polymorphic variants of DNA damage repair genes play a role in the susceptibility to NSCL/P. BRIP1 might be novel candidate gene for this common developmental anomaly.

Keywords: BLM; BRIP1; DNA damage repair; E2F1; NSCL/P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cleft Lip / genetics*
  • Cleft Lip / pathology
  • Cleft Palate / genetics*
  • Cleft Palate / pathology
  • DNA Damage
  • DNA Repair*
  • DNA-Binding Proteins / genetics*
  • E2F1 Transcription Factor / genetics
  • Fanconi Anemia Complementation Group Proteins
  • Female
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Models, Genetic
  • Odds Ratio
  • Polymorphism, Genetic*
  • RNA Helicases / genetics*
  • RecQ Helicases / genetics


  • DNA-Binding Proteins
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Fanconi Anemia Complementation Group Proteins
  • Bloom syndrome protein
  • RecQ Helicases
  • BRIP1 protein, human
  • RNA Helicases