Investigation of polymorphisms in BMP2, BMP4, SMAD6 and RUNX2 genes and pulp stones.

This study aimed to assess the association between genetic polymorphisms in BMP2 (rs1005464 and rs235768), BMP4 (rs17563), SMAD6 (rs2119261 and rs3934908) and RUNX2 (rs59983488 and rs1200425) and pulp stones (PS). A total of 117 participants, consisting of 63 individuals with PS and 54 without PS, were included. Digital radiographs and a demographic/clinical questionnaire were used. Genomic DNA from salivary cells was genotyped via real-time polymerase chain reaction. Statistical analyses, including Chi-Square, Fisher's exact tests, Poisson regression and dimensionality reduction, were conducted. The rs2119261 polymorphism in the SMAD6 gene showed an association with genotype distribution in the recessive model (p = 0.049). The T-T haplotype in the SMAD6 gene (rs2119261 and rs3934908) was more prevalent in the control group and significantly linked with PS (p = 0.029). No associations were found between PS risk and genetic polymorphisms in BMP2, BMP4 and RUNX2. Polymorphisms in the SMAD6 gene were associated with PS.

Assessing the prevalence of S-shaped root canal and associated genes in humans.

BACKGROUND: Multiple signaling molecules have been shown to play crucial roles in dental root development. Therefore, we aimed to investigate the prevalence of S-shaped roots and also to investigate, if single nucleotide polymorphisms (SNPs) in BMP2, BMP4 and SMAD6 are associated with this phenotype in humans. METHODS: This is a cross-sectional phenotype-genotype association study that used radiographs to determine the phenotypes and DNA to investigate SNPs in candidate genes. During the radiographic exam, teeth presenting root canal(s) doubly curved were considered S-shaped roots. SNPs in BMP2 (rs1005464 and rs235768), BMP4 (rs17563) and SMAD6 (rs2119261 and rs3934908) were blindly genotyped by real-time PCR using TaqMan assay. The relative and absolute frequency of S-shaped roots were calculated. Chi-square test was used to compare the genotype distributions between control and S-shaped groups. RESULTS: Among the 578 subjects, 61 (10.6 %) presented at least one tooth with an S-shaped root. The most commonly affected type of tooth was the premolar. rs1005464 in BMP2 was statistically associated with an S-shaped root (p = 0.036). rs235768 in BMP2 was associated with an S-shaped root also in mandibular teeth (p = 0.017). A statistical significance was observed for the rs3934908 in SMAD6 (p = 0.049) for S-shaped root in the mandible. In the analysis stratified according to the type of tooth, rs235768 in BMP2 was associated with S-shaped roots in premolars (p = 0.029). CONCLUSION: The prevalence of S-shaped roots is 10.6 % in permanent teeth. SNPs in BMP2 and SMAD6 could be involved in a higher chance to present S-shaped roots.

Genetic variants in bone morphogenetic proteins signaling pathway might be involved in palatal rugae phenotype in humans.

This study investigated, if genetic variants in BMP2, BMP4 and SMAD6 are associated with variations in the palatal rugae pattern in humans. Dental casts and genomic DNA from 75 patients were evaluated. Each patient was classified as follows: total amount of rugae; bilateral symmetry in the amount, length and shape of the palatal rugae; presence of secondary or fragmentary palatal rugae; presence of unifications; predominant shape; and predominant direction of the palatal rugae. The genetic variants in BMP2 (rs1005464 and rs235768), BMP4 (rs17563) and SMAD6 (rs2119261 and rs3934908) were genotyped. Genotype distribution was compared between palatal rugae patterns using the chi-square test (alpha = 0.05). The allele A was associated with the presence of secondary or fragmentary rugae for rs1005464 (OR = 2.5, 95%CI 1.1-6.3; p = 0.014). Secondary or fragmentary rugae were associated with the G allele in rs17563 (OR = 2.1, 95%CI 1.1-3.9; p = 0.017). rs17563 was also associated with rugae unification (p = 0.017 in the additive model). The predominant shape (wavy) was associated with rs2119261 (p = 0.023 in the additive model). The left-right symmetry of the length of primary rugae was associated with rs3934908 in the recessive model (OR = 3.6, 95%CI 1.2-11.7; p = 0.025). In conclusion, genetic variants in the BMP pathway impacted on palatal rugae pattern.

Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients.

BACKGROUND: To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). PATIENTS AND METHODS: We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR) to asses the pattern of TGFbeta1, TGFbeta2, TGFbeta3 in oral SCC. RESULTS: Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively). In addition, simultaneously Smad2- and Smad6+ oral SCC group of patients did not reach median overall survival (mOS) whereas the mOS of Smad2+/Smad6- subgroup was 11.6 months (P = 0.004, univariate analysis). Regarding to TGFbeta isoforms, we found that Smad2 mRNA and TGFbeta1 mRNA were inversely correlated (p = 0.05, R = -0.33), and that seven of the eight TGFbeta1+ patients were Smad2-. In larynx SCC, Smad7- patients did not reach mOS whereas mOS of Smad7+ patients were only 7.0 months (P = 0.04). No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. CONCLUSION: Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFbeta signaling should be better clarified in the future.

Genetic susceptibility to keloid scarring: SMAD gene SNP frequencies in Afro-Caribbeans.

Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The increased familial clustering in KD, its increased prevalence in certain races and increased concordance in identical twins suggest a strong genetic predisposition to keloid formation. The highest incidence of keloids is found in the black population, where it has been estimated around 4-6% and up to 16% in random samples of black Africans. SMAD genes 3, 6 and 7 were investigated as candidate genes in Jamaican patients with keloid scars (n = 183) and a matched control population (n = 121) because of their previously reported involvement in fibrotic disorders and to determine if they were associated with keloid disease susceptibility. Thirty Five SNPs across these genes were genotyped using Time-of-Flight Mass Spectrometry (MALDI-TOF MS) and iPLEX assay. Linkage disequilibrium (LD) was established between several of the SNPs investigated. In the Jamaican population, the SMAD SNPs investigated for this study were not strongly associated with increased risk of developing KD. Identification of genetic markers in candidate genes such as the SMAD family may be of significant importance in diagnosis, prognosis and development of new therapies in the management of keloid scarring.