Natural Resistance Associated Macrophage Protein 1 Gene Polymorphism is Associated with Chronic Periodontitis Not Peri-Implantitis in an Iranian Population: A Cross Sectional Study.

In inflammatory diseases such as peri-implantitis (PI) and chronic periodontitis (CP) both adaptive and innate immunity play a part. Natural resistance associated macrophage protein 1 (NRAMP1) has considerable effects on macrophage function (phagocytosis) and host innate immune response against infections. The present study was to investigate the relationship of NRAMP1 gene polymorphisms with PI and CP in an Iranian population. In this cross sectional study 79 patients with CP, 38 patients with PI and 84 healthy controls presenting to the Periodontology Department of Shahid Beheshti University of Medical Sciences were enrolled. DNA was extracted from fresh blood samples of arm vein of participants and transferred to KBiosience institute (United Kingdom) for genotyping. X2 and Fisher's exact tests were used by SPSS software v.19 for statistical analyzes. Significant differences were detected in the distribution of genotypes between control and CP groups both for rs17235409 and rs2276631 polymorphisms (P:0.044 and P:0.028 respectively). Distribution of genotypes differed insignificantly in comparison of PI and control groups for rs2276631 (P:0.623) and either rs17235409 (P:1) polymorphisms. Based on our results, we conclude that presence of G allele in both rs2276631 and rs17235409 location may be a protective factor against CP. More studies with a larger sample size in different populations are required for confirming NRAMP1 as a genetic determinant in periodontal disorders.

Gene polymorphisms of TNF-α and IL-1ß are not associated with generalized aggressive periodontitis in an Iranian subpopulation.

Cytokines play a part in pathogenesis of periodontitis via inflammation phenomenon. Aggressive periodontitis (AgP) is a multifactorial disease resulting in rapid tooth loss due to severe destruction of tooth supporting apparatus. Recently, researchers have focused on genetic susceptibility of periodontitis through investigating the gene variations of cytokines and other components of immune response. In this study we analyzed single nucleotide polymorphism (SNP) of two cytokines in association with AgP in an Iranian-khorasanian population; Interleukin-1 beta (IL-1ß) +3954 C/T and Tumor Necrosis Factor alpha (TNF-α) -308 G/A. From arm vein of patients (n=58) and periodontally healthy individuals (n=60) blood sample was obtained and the DNA was extracted. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) procedure was performed to recognize the SNPs. X2 test was used to determine the statistically significant differences between the two groups. The frequency of genotypes and alleles had no significant differences between patients and control groups. The distributions were as follows. IL-1ß +3954: CT, CC and TT genotypes in patients were 39.6%, 60.4% and 0.0% and in controls were 41.7%, 50% and 8.3%, respectively. TNF-α -308: GA, GG and AA genotypes in patients were 44.8%, 41.4% and 13.8% and in controls were 46.7%, 50% and 3.3%, respectively.This investigation do not substantiates the role of IL-1ß +3954 and TNF-α -308 polymorphisms, separately, as risk determinants for AgP in Iranian population. Further research based on all components of immune response, is needed to corroborate the genetic susceptibility of AgP.

Hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) polymorphism is associated with chronic inflammatory periodontitis. A cross-sectional study.

BACKGROUND: Chronic periodontitis (CP) and peri-implantitis (PI) are inflammatory diseases that affect supporting tissues of teeth or implants. The involvement of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) in neuronal excitability, hyperalgesia, allodynia, spontaneous pain, synaptic plasticity, and rebound activity was previously determined. Recently, scientists found that HCN2 plays an important role in chronic inflammatory pain. This study aimed to evaluate the relationship between gene polymorphisms of HCN2 and CP/PI. METHODS: A total of 74 patients with CP, 37 patients with PI, and 80 healthy controls presenting to the Periodontology Department of Shahid Beheshti University of Medical Sciences were enrolled. DNA was extracted from fresh blood samples of the arm vein of participants and transferred to KBioscience Institute (UK) for genotyping. χ2-test was performed with SPSS software v.19 for statistical analyses. A p value <0.05 was considered significant. RESULTS: Both rs55687900 and rs148730222 had significant differences in genotype frequencies between CP and healthy groups (p=0.005 and 0.006, respectively). The allele frequencies also revealed significant frequencies (p=0.004 and 0.006, respectively). The comparison of genotype and allele frequencies between PI and healthy groups had no significant difference. CONCLUSIONS: HCN2 polymorphism may play a role in CP but not in PI. Despite this approval, more studies with larger sample sizes in different populations are necessary.

BRAF gene polymorphism (rs10487888) assessment in chronic periodontitis and peri-implantitis in an Iranian population.

BACKGROUND: Peri-implantitis (PI) and chronic periodontitis (CP) are multifactorial diseases of implant/tooth supporting tissue that are caused by bacterial infection and increased host immune response. T-cell proliferation plays a pivotal role in the orchestration of host response to bacterial infection. BRAF is a positive regulator of T-cell proliferation. The aim of this study was to evaluate for the first time the role of a functional single nucleotide polymorphism (SNP) of the BRAF gene in association to PI and CP. METHODS: A total of 194 individuals referred to the Periodontology Department of Shahid Beheshti Dental School, Tehran, Iran, were divided into three groups: 74 patients in the CP group (39 men and 35 women, with mean age of 48.3 years), 38 patients in the PI group (20 men and 18 women, with mean age of 50.2 years), and 82 patients in the healthy periodontium group (39 men and 43 women, with mean age of 45.4 years). DNA was extracted from fresh blood samples collected from the arm vein of participants and was transferred to KBiosience institute (United Kingdom) for genotyping. χ2 and Kruskal-Wallis tests were conducted using SPSS software v. 19 for statistical analysis (p<0.05). RESULTS: The allele (C/T) and genotype (CC, CT, TT) frequencies had insignificant differences among the three groups; however, the CC genotype was more prevalent in the healthy condition than in the disease conditions. CONCLUSIONS: The BRAF gene polymorphism (rs10487888) may not be a genetic determinant for increasing the risk of CP and PI among the Iranian population. More studies with more sample size in different populations are necessary for determining the effect of this SNP.

Analysis of RANKL gene polymorphism (rs9533156 and rs2277438) in Iranian patients with chronic periodontitis and periimplantitis.

OBJECTIVE: RANK/OPG/RANKL pathway plays a significant role in osteoclastogenesis, osteoclast activation, and regulation of bone resorption. The aim of this study was to investigate the association of RANKL gene polymorphisms (rs9533156 and rs2277438) with chronic periodontitis and peri-implantitis in an Iranian population. DESIGN: 77 patients with chronic periodontitis, 40 patients with peri-implantitis and 89 periodontally healthy patients were enrolled in this study. 5cc of blood was obtained from the cephalic vein of subjects arms and transferred into tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP) technique. Differences in the frequencies of genotypes and alleles in the disease and control groups were analyzed using Chi-square and Fisher's exact statistical tests. RESULTS: Comparison of frequency of alleles in SNP rs9533156 of RANKL gene between the chronic periodontitis group with the control and peri-implantitis groups revealed statistically significant differences (P=0.024 and P=0.027, respectively). Comparison of genotype expression of SNP rs9533156 on RANKL gene between the peri-implantitis group with chronic periodontitis and control groups revealed statistically significant differences (P=0.001); the prevalence of CT genotype was significantly higher amongst the chronic periodontitis group. Regarding SNP rs2277438 of RANKL gene, comparison of prevalence of genotypes and frequency of alleles did not reveal any significant differences (P=0.641/P=0.537, respectively). CONCLUSIONS: The results of this study indicate that CT genotype of rs9533156 RANKL gene polymorphism was significantly associated with peri-implantitis, and may be considered as a genetic determinant for peri-implantitis.

Analysis of osteoprotegerin (OPG) gene polymorphism in Iranian patients with chronic periodontitis and peri-implantitis. A cross-sectional study.

PURPOSE: Receptor activator for nuclear factor kappa B ligand (RANKL)/RANK/OPG pathway plays a redundant role in osteoclastogenesis, osteoclast activation and regulation of bone resorption. Recently, single nucleotide polymorphisms (SNP) have been reported as a co-factor in pathogenesis of inflammatory diseases. The aim of this study was to investigate the relationship between osteoprotegerin (OPG) gene polymorphisms and chronic periodontitis and peri-implantitis in an Iranian population. MATERIALS AND METHODS: 77 patients with chronic periodontitis (CP), 40 patients with peri-implantitis (PI) and 89 periodontally healthy subjects were enrolled in this study. A total of 5 ml of blood was obtained from the arm vein of participants. DNA was extracted based on the salting out method. Two functional SNPs (T950C and G1181C) were analysed by using polymerase chain reaction and restriction fragment length polymorphism (PCR_RFLP). The prevalence differences in three batches were evaluated by chi-square test. RESULTS: An evaluation of the T950C genotype found that there was no statistical difference between groups. A comparison of the G1181C genotype distribution between peri-implantitis and chronic periodontitis groups, and between peri-implantitis and normal groups found that the frequency of the CC genotype was significantly higher in patients with peri-implantitis (P = 0.005). CONCLUSIONS: Our results indicate that a SNP at G1181C is associated with the presence of PI.