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Hedgehog signaling pathway and vitamin D receptor gene variants as potential risk factors in odontogenic cystic lesions

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Abstract

Objectives

Genetic variants in the hedgehog signaling pathway and VDR gene are involved in inflammatory responses and neoplastic transformation. Current study investigated whether single-nucleotide polymorphisms in the hedgehog pathway genes PTCH1, GLI1, SMO, and VDR contribute to susceptibility to odontogenic cystic lesions, odontogenic keratocysts, or inflammatory radicular cysts.

Material and methods

Current study examined polymorphisms of PTCH1 (rs357564) and PTCH1 insertion (IVS1-83), GLI1 (rs2228224, rs2228226), SMO (rs2228617), and VDR (rs2228570, rs731236, rs7975232). A case-control study was conducted on 41 keratocyst cases, 43 radicular cyst cases, and control group of 93 healthy individuals without cystic lesions, radiographically confirmed. Single-nucleotide polymorphisms were assessed by real-time and TaqMan SNP genotyping assays, while PTCH1 insertion 18 bp IVS1-83 polymorphism was determined by PCR.

Results

The difference in genotype distribution between keratocyst cases and control group was observed for PTCH1 IVS1-83 and GLI1 rs2228224 polymorphism (p = 0.022, p = 0.030, respectively). Homozygous mutant GG genotype within GLI1 rs2228224 is associated with increased susceptibility for odontogenous keratocysts, with adjusted odds ratio of 4.098 (confidence interval of 1.482–11.328, p = 0.007).

Conclusion

GLI1 rs2228224 and PTCH1 polymorphisms could predispose to odontogenic keratocysts.

Clinical relevance

Variants in hedgehog signaling pathway genes, such as GLI1 and PTCH1, and vitamin D receptor gene, might be considered as molecular risk factors in odontogenic cystic lesions and potential targets for novel therapeutic approaches.

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Funding

The work was supported by the Faculty of Medicine, Military Medical Academy, Belgrade, Serbia; Grant: MFVMA/11/16-18.

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Authors and Affiliations

  1. Department of Oral Surgery, School of Dentistry, University of Belgrade, Belgrade, Serbia

    Marko Magic, Jelena Stepic, Marko Pejovic & Snjezana Colic

  2. Faculty of Biology, University of Belgrade, Belgrade, Serbia

    Katarina Zeljic

  3. Institute for Medical Research, Military Medical Academy, Belgrade, Serbia

    Stevo Jovandic, Zvonko Magic & Gordana Supic

  4. University of Defence, Faculty of Medicine, Military Medical Academy, Crnotravska 17, Belgrade, 11000, Serbia

    Zvonko Magic & Gordana Supic

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  1. Marko Magic
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  2. Katarina Zeljic
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Correspondence to Gordana Supic.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Supplemental Figure 1

Graphical Fruchterman-Rheingold diagram of statistical epistatic interactions between analyzed polymorphisms in PTCH, GLI1, SMO, and VDR gene variants in a) keratocysts and controls b) radicular cysts and controls. Diagram was constructed by using MDR v.3.0.2 software. Red and orange lines represent synergistic interactions; yellow and green represent/indicate weak interactions and blue lines indicate redundancy. (PNG 3226 kb)

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Magic, M., Zeljic, K., Jovandic, S. et al. Hedgehog signaling pathway and vitamin D receptor gene variants as potential risk factors in odontogenic cystic lesions. Clin Oral Invest 23, 2675–2684 (2019). https://doi.org/10.1007/s00784-018-2686-5

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