Jumana A. Karasneh

Association of interleukin-10 gene promoter polymorphisms with chronic and aggressive periodontitis.

OBJECTIVE Interleukin-10 gene promoter polymorphisms have been associated with interleukin-10 decreased production, thereby playing a role in the pathogenesis of periodontitis. This study aimed to investigate whether interleukin-10 single nucleotide polymorphisms at positions -1087(G/A) and -597(C/A) are associated with generalised chronic periodontitis and localised aggressive periodontitis. METHODS Genomic DNA samples were isolated from 276 unrelated Jordanian participants. Subjects were categorised into 86 periodontally healthy controls, 105 chronic periodontitis patients and 85 localised aggressive periodontitis patients. Genotype frequencies were calculated, and differences were determined using Pearson chi-squared test, and odds ratio and 95% confidence intervals were included. RESULTS The frequencies of the -1087A and -597A alleles were significantly more common in chronic periodontitis patients than controls. The A-positive allele genotypes (GA, AA) at position -1087 and A-positive allele genotypes (CA, AA) at position -597 appeared to increase the risk of having chronic periodontitis. No significant differences were observed in the genotype frequencies between localised aggressive periodontitis patients and controls. CONCLUSIONS These findings indicate the possible use of interleukin-10 single nucleotide polymorphisms as genetic markers in chronic periodontitis patients and further emphasise the molecular differences between chronic periodontitis and aggressive periodontitis.

Investigation of the interleukin-1 gene cluster polymorphisms in Jordanian patients with chronic and aggressive periodontitis.

OBJECTIVE Interleukin-1 (IL-1) is a proinflammatory cytokine that is highly elevated in response to bacterial biofilms and is a potential risk factor for periodontal diseases. IL-1 gene polymorphisms have been associated with the IL-1 level. The aim of this study was to investigate if IL-1 gene cluster polymorphisms are associated with chronic (CP) and aggressive (AgP) periodontitis in a Jordanian population. METHODS A total of 100 CP, 80 AgP patients and 80 controls were genotyped using PCR for IL-1RN-86-bp VNTR and PCR-RFLP for IL-1A-889, IL-1B-511, -35, +3953, and IL-1RN +8006, +9589, +11100 SNPs. The distribution of alleles and genotypes between groups was compared using χ(2) analysis. Estimation of haplotype frequencies was carried out using the EH programme. RESULTS The IL-1RN8006 SNP and the IL-1RN-VNTR were associated with CP but not with AgP. The C allele and TC genotype of IL-1RN8006 were increased in CP (P(corr)=0.002, 0.00026 respectively). The A1 allele and A1/A1 genotype of the IL1-RN-VNTR were significantly increased in CP (P(corr)=0.0007, <0.0001 respectively). The CA1 haplotype formed by both markers was present in 29 CP patients but not in any of the controls (P<0.0001). No significant differences were found in the distribution of allele and genotype frequencies of the other markers between CP and AgP cases and controls. CONCLUSIONS IL-1RN 8006 and IL-1RN VNTR were associated with CP but not AgP in a Jordanian population, whilst other investigated markers in IL-1A, IL-1B and IL-1RN were not associated with either CP or AgP.

Association of vitamin D receptor gene polymorphisms with chronic and aggressive periodontitis in Jordanian patients

Vitamin D acts through binding with vitamin D receptor (VDR) and is responsible for regulating bone metabolism and mineralization; it also suppresses the immune system. The aim of this study was to investigate if VDR gene polymorphisms are associated with chronic periodontitis (CP) and aggressive periodontitis (AgP) in a Jordanian population. A total of 99 patients with CP, 63 patients with AgP, and 126 controls were genotyped using PCR-restriction fragment length polymorphism (RFLP) for BsmI, ApaI, and TaqI single nucleotide polymorphisms (SNPs). The association was determined after correcting for confounding factors using multivariate logistic regression analysis. Estimation of haplotype frequencies was carried out using the EH program, and haplotypes were constructed using the phase 2.1 program. After correcting for confounding factors, multivariate logistic regression analysis revealed that inheritance of the BsmI bb genotype or the ApaI aa genotype was associated with increased risk of developing CP (OR = 2.4 and OR = 3.4, respectively) but with reduced risk of developing AgP (OR = 0.4 and OR = 0.3, respectively). This was further supported by association of the ba haplotype with CP but not with AgP. This study supports an association of VDR gene polymorphisms with CP and AgP in a Jordanian population; however, the pattern of association was different between the two diseases.

Association between recurrent aphthous stomatitis and inheritance of a single‐nucleotide polymorphism of the NOS2 gene encoding inducible nitric oxide synthase

BACKGROUND  Recurrent aphthous stomatitis is a common ulcerative disease of the oral mucosa. Recurrent oral aphthous ulceration is also a feature of the more serious and systemic Behçets disease. Nitric oxide is a free radical synthesized by one of a family of nitric oxide synthase (NOS) enzymes and is an important regulator of inflammation and immunity. Association of NOS3 gene polymorphisms encoding endothelial nitric oxide synthase has been reported in Behçets disease but not recurrent aphthous stomatitis. The aim of this study was to investigate any association between NOS2 gene polymorphisms that encode inducible nitric oxide synthase and recurrent aphthous stomatitis. METHODS  This is a case control association study. Eighty-three Jordanian recurrent aphthous stomatitis patients and 83 age, gender and ethnically matched controls were genotyped for three NOS2 single-nucleotide polymorphisms, rs10459953, rs1060822 and rs2297518. Chi-squared analysis was used to compare the allele frequencies and genotypes. RESULTS  There was a significant association between recurrent aphthous stomatitis and inheritance of single-nucleotide polymorphism rs2297518 (P = 0.006). Although no direct association was demonstrated between rs10459953 or rs1060822 and recurrent aphthous stomatitis, a strong linkage disequilibrium was identified between rs1060822 and rs2297518. CONCLUSION  Inheritence of a NOS2 single-nucleotide polymorphism rs2297518 is associated with increased risk of recurrent aphthous stomatitis in a Jordanian population. Confirmatory studies in other populations and investigation of other NOS2 gene polymorphisms will enhance our understanding of the functional basis of this association and help elucidate the role of inducible nitric oxide synthase in recurrent aphthous stomatitis.

The association of aggressive and chronic periodontitis with systemic manifestations and dental anomalies in a jordanian population: a case control study

BackgroundThe relationship between dental anomalies and periodontitis has not been documented by earlier studies. Although psychological factors have been implicated in the etiopathogenesis of periodontitis, very little information has so far been published about the association of anxiety and depression with aggressive periodontitis. The aim of this study was to investigate the association of chronic periodontitis and aggressive periodontitis with certain systemic manifestations and dental anomalies.MethodsA total of 262 patients (100 chronic periodontitis, 81 aggressive periodontitis and 81 controls), attending the Periodontology clinics at Jordan University of Science and Technology, Dental Teaching Centre) were included. All subjects had a full periodontal and radiographic examination to assess the periodontal condition and to check for the presence of any of the following dental anomalies: dens invaginatus, dens evaginatus, congenitally missing lateral incisors or peg-shaped lateral incisors. Participants were interrogated regarding the following: depressive mood, fatigue, weight loss, or loss of appetite; and their anxiety and depression status was assessed using the Hospital Anxiety and Depression (HAD) scale.ResultsPatients with aggressive periodontitis reported more systemic symptoms (51%) than the chronic periodontitis (36%) and control (30%) patients (p < 0.05). Aggressive periodontitis patients had a higher tendency for both anxiety and depression than chronic periodontitis and control patients. Dental anomalies were significantly (p < 0.05) more frequent among both of chronic and aggressive periodontitis patients (15% and 16%, respectively), compared to controls.ConclusionIn this group of Jordanians, systemic symptoms were strongly associated with aggressive periodontitis, and dental anomalies were positively associated with both aggressive and chronic periodontitis.

TLR2, TLR4 and CD86 gene polymorphisms in recurrent aphthous stomatitis

BACKGROUND Recurrent aphthous stomatitis (RAS) is an inflammatory disease induced by genetic and environmental factors. Toll-like receptor (TLR) and CD86 are essential components for innate immunity and cellular immune response. We aimed to determine whether inheritance of specific TLR2, TLR4and CD86 gene polymorphisms are associated with RAS. METHODS Ninety-six patients with RAS and 153 controls were studied. Eight SNPs were genotyped using PCR-RFLP technique; four in TLR2 gene: rs4696480, rs3804100, rs121917864, rs5743708; three in TLR4 gene: rs10759931, rs4986790 rs1927911; and one in CD86 gene rs17281995. Association was assessed by logistic regression analysis. Linkage disequilibrium (LD) was assessed using the Haploview program. RESULTS Significant increase in inheritance of A allele (OR = 1.6, P = 0.01) and AA genotype (OR = 3.89, P = 0.01) of TLR4 rs10759931 was observed in cases. TLR4rs1927911 C allele and CC genotype were also increased (OR = 1.60 and 2.78 respectively); however, this was not statistically significant (P = 0.02 and 0.03 respectively). TLR2 and CD86 did not show association with RAS. CONCLUSIONS This is the first study to investigate the association of TLR and CD86 with RAS. We found a significant association between TLR4 rs10759931 polymorphism and RAS. Confirmatory studies in other populations and functional investigations are needed to determine the role of TLR4 in RAS.

Endothelial nitric oxide synthase gene polymorphisms are not associated with recurrent aphthous stomatitis

OBJECTIVE Recurrent aphthous stomatitis (RAS) is a common ulcerative disease of the oral mucosa. Recurrent oral aphthous ulceration is the most common and consistent feature of the more serious and systemic Behçets disease (BD). Association of endothelial nitric oxide synthase (eNOS) gene polymorphisms with BD have been reported in different populations. This study aims to investigate if there is an association between these polymorphisms and RAS. METHODS A case-control association study using 91 Caucasoid RAS patients and 91 ethnically matched systemically healthy controls were genotyped for the -786 and 894 eNOS single nucleotide polymorphisms (SNPs) and a variable number of tandem repeat (VNTR) polymorphism. Chi-square analysis was used to compare the allele and genotype frequencies. RESULTS No significant difference was found in the distribution of allele and genotype frequencies of the -786 and +894 polymorphisms or the VNTR polymorphism between cases and controls. CONCLUSION eNOS gene polymorphisms associated with BD are not associated with RAS. This suggests that the oral ulceration common to both conditions may have a different underlying genetic aetiology. Although our data suggests that RAS does not have an association with eNOS, it is still possible that nitric oxide is involved in the disease process. This could still occur through localised and inflammation driven regulation by iNOS.

Modified protocol including topical minocycline in orabase to manage medication‐related osteonecrosis of the jaw cases

OBJECTIVE Management of medication-related osteone-crosis of the jaw (MRONJ) with active infection can be a serious challenge for clinicians. Based on Association of Oral and Maxillofacial Surgeons (AAOMS) recommendations, we have tested a modified treatment protocol using topical minocycline. STUDY DESIGN Five patients diagnosed with stage II or III MRONJ lesions were willing to consent to our protocol. In addition to conventional treatment as suggested by the AAOMS, such as, surgical debridement, chlorhexidine irrigation, and systemic antibiotics, we applied 10% minocycline to the lesions once a week for sustained local antibiotic delivery. RESULTS All five patients reported pain relief after the first minocycline application. Complete healing occurred in three patients; case three healed completely after the third application, one case continues to improve toward resolution and one withdraws due to other non-relevant medical problem. CONCLUSIONS In this study, we are reporting favorable results using a modified protocol with topical minocycline to treat MRONJ lesions.

Effect of cigarette smoking on subgingival bacteria in healthy subjects and patients with chronic periodontitis

BackgroundCigarette smoking is known to increase the risk of periodontal destruction and developing chronic periodontitis (CP). It is also reported to affect the subgingival bacterial profile among CP patients. However, studies on the effect of smoking on the bacterial profile among healthy subjects are still limited. Therefore, the aim of this study was to investigate the impact of smoking on the subgingival bacterial profile in both healthy adults and CP patients.MethodsSubgingival plaque samples were collected from CP patients (30 nonsmokers and 9 smokers) and healthy subjects (37 non-smokers and 18 smokers). Genomic DNA was extracted and 25 bacterial species were detected using PCR of 16S rRNA. Comparing smokers to non-smokers from each group was conducted using chi2 and binary logistic regression analysis.ResultsAfter correcting for confounding factors, the odds of having Slackia exigua, Selenomonas sputigena and Campylobacter rectus was higher among healthy smokers (ORadj = 10.1, 6.62 and 5.62 respectively). While for CP group, the highest odds were observed for Treponema amylovorum, Treponema medium, Slackia exigua and Treponema vincentii (ORadj = 20.7, 7.97, 6.37 and 5.37 respectively) and the increase in Treponema amylovorum was statistically significant (p = 0.05).ConclusionSmoking affects the subgingival bacterial profile in healthy individuals and is responsible for the depletion of beneficial bacteria and the increase in periodontopathogenic bacteria. In the CP patient group, our study suggests that subgingival bacteria (particularly Treponema species) make a more substantial contribution in the etiology of CP among non-smokers. Further studies using a larger sample set and more sensitive and quantitative techniques (such as real -time PCR) are needed to enhance our understanding of the exact effect of smoking on subgingival biofilm.

Lack of Utility of Cytokeratins in Differentiating Pseudocarcinomatous Hyperplasia of Granular Cell Tumors from Oral Squamous Cell Carcinoma.

Granular cell tumor (GCT) of the oral cavity is a benign lesion. Half of oral GCTs demonstrate pseudocarcinomatous hyperplasia (PCH) of the mucosa which can mimic invasive islands of oral squamous cell carcinoma (SCC). Such similarity can be confusing when diagnosing or evaluating the two conditions, potentially leading to misdiagnosis or misclassification. Indeed, several misdiagnosed cases of oral GCT have been reported in the literature as OSCC or malignant oral GCT that resulted in unnecessary aggressive treatment for the affected patients. The aim of this study was to investigate if the cytokeratin pattern of the PCH can help in differentiating GCT from oral SCC. To distinguish between these two entities, we examined 12 patient specimens of oral GCT-PCH and oral SCC histologically and via immunohistochemistry (IHC) for CK13, CK17 and P75. The results suggest that the cytokeratin profile of PCH is similar to that of oral SCC. Therefore, consideration of IHC findings for epithelial markers alone may lead to erroneous diagnosis; thus, the presence of the granular tumor underneath the PCH and its immunopositivity for P75 or other neural definition markers can be essential to identify the underlying tumor and exclude oral SCC. Finally we recommend more studies on the molecular biology of PCH to understand how it can mimic oral SCC histologically without harboring its malignant phenotype clinically, which could have significant translational potential for understanding invasive oral SCC.