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

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.