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

Agnieszka Gaczkowska; Kamil K. Hozyasz; Piotr Wójcicki; Barbara Biedziak; Paweł P. Jagodziński; Adrianna Mostowska

doi:10.20883/jms.2016.1

Authors

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

DOI:

https://doi.org/10.20883/jms.2016.1

Keywords:

NSCL/P, DLX1, polymorphism, haplotype

Abstract

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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