Polymorphic variants in the DLX1 gene and the risk of non-syndromic cleft lip with or without cleft palate

  • Agnieszka Gaczkowska Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland
  • Kamil K. Hozyasz Department of Pediatrics, Institute of Mother and Child, Warsaw, Poland
  • Piotr Wójcicki University Clinic of Medical Academy in Wroclaw and Department of Plastic Surgery Specialist Medical Center in Polanica Zdroj, Poland
  • Barbara Biedziak Department and Clinic of Dental Surgery, Poznan University of Medical Sciences, Poland
  • Paweł P. Jagodziński Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland
  • Adrianna Mostowska Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland
Keywords: NSCL/P, DLX1, polymorphism, haplotype


Background. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common developmental anomaly, which etiology is complex and not completely elucidated.Aim. The aim of the present study was to evaluate whether common polymorphisms in the distal-less homeobox gene 1 (DLX1) may contribute to the risk of orofacial clefts in the Polish population.Material and methods. Five single nucleotide variants were genotyped using high-resolution melting curve analysis in a group of 278 patients with NSCL/P and properly matched controls (n = 574).Results. Statistical analysis revealed that two variants located in the 3’ untranslated region of DLX1, rs788172 and rs788173, were associated with a decreased risk of NSCL/P (ptrend = 0.041 and ptrend = 0.025, respectively). The allelic frequencies for these polymorphisms were significantly lower in patients compared to healthy individuals (p = 0.040 and p = 0.024, respectively). However, all these results did not remain statistically significant after applying the Bonferroni correction for multiple comparisons. The results of single-marker analysis for DLX1 were confirmed by haplotype analysis. The best evidence of the haplotype association with the risk of NSCL/P was observed for the T-G-G haplotype consisting of rs1047889, rs788172 and rs788173 major alleles. This high risk haplotype was more frequent among cases than controls (p = 0.013, pcorrected = 0.026).Conclusions. We found evidence for the association between DLX1 gene variants and the risk of NSCL/P in the Polish population. To confirm our preliminary findings further, larger sample size studies are required.


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How to Cite
Gaczkowska, A., Hozyasz, K., Wójcicki, P., Biedziak, B., Jagodziński, P., & Mostowska, A. (2016). Polymorphic variants in the DLX1 gene and the risk of non-syndromic cleft lip with or without cleft palate. Journal of Medical Science, 85(1), 7-14. https://doi.org/10.20883/jms.2016.1
Original Papers