Clinical oral investigations · 2018
Hedgehog signaling pathway and vitamin D receptor gene variants as potential risk factors in odontogenic cystic lesions.
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Magic Marko, Zeljic Katarina, Jovandic Stevo, Stepic Jelena, Pejovic Marko, Colic Snjezana, Magic Zvonko, Supic Gordana
Аннотация
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.
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.