|
 
 |
| REVIEW ARTICLE |
|
| Year : 2014 | Volume
: 2
| Issue : 1 | Page : 3-7 |
|
Single nucleotide polymorphisms and periodontitis
Ramalingam Karthikeyan1, Syed Wali Peeran2, Manohar Murugan3, Khaled Awidat4, Omar Basheer5, Marei Hamad Al Mugrabi6
1 Department of Oral Pathology and Microbiology; Department of Orthodontics, Faculty of Dentistry, Sebha University, Sebha Sebha University, Sebha, Libya
2 Department of Orthodontics, Faculty of Dentistry; Department of Periodontology and Implantology, Sebha University, Sebha Sebha University, Sebha, Libya
3 Department of Microbiology, Faculty of Medicine, Sebha University, Sebha, Libya
4 Department of Orthodontics, Faculty of Dentistry, Sebha University, Sebha, Libya
5 Department of Oral and maxillofacial surgery, Sebha University, Sebha, Libya
6 Department of Periodontics, Faculty of Dentistry, Benghazi University, Benghazi, Libya
| Date of Web Publication | 28-Apr-2014 |
Correspondence Address:
Ramalingam Karthikeyan
Department of Oral Pathology and Microbiology, Faculty of Dentistry, Sebha University, Sebha
Libya
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2348-1471.131556
The susceptibility to various diseases is studied with association to genetic polymorphisms. Among these polymorphisms, single-nucleotide polymorphisms (SNPs) are very common throughout the genome. The recent advances in genetic assay techniques and increase in SNP databases are paving a way for investigation of susceptibility genes for periodontitis. This article attempts to review the role of SNP and its implications in periodontal disease and management. Keywords: Aggressive, chronic, periodontitis, single-nucleotide polymorphisms
How to cite this article:
Karthikeyan R, Peeran SW, Murugan M, Awidat K, Basheer O, Al Mugrabi MH. Single nucleotide polymorphisms and periodontitis. Dent Med Res 2014;2:3-7 |
How to cite this URL:
Karthikeyan R, Peeran SW, Murugan M, Awidat K, Basheer O, Al Mugrabi MH. Single nucleotide polymorphisms and periodontitis. Dent Med Res [serial online] 2014 [cited 2023 Mar 31];2:3-7. Available from: https://www.dmrjournal.org/text.asp?2014/2/1/3/131556 |
| Introduction | |  |
Periodontitis, an oral inflammatory disease with destruction of periodontal tissues, is a complex disease associated with multiple genetic factors and oral environmental factors. [1] Periodontal disease is regarded as a multifactorial condition that occurs because of interplay between environmental, behavioral, microbial and genetic factors. Genetic studies have revealed the polygenic nature of chronic periodontitis. [2]
SNPs are DNA sequence variations that result from the alteration of a single nucleotide, and some SNPs are population-specific. SNPs in these genes do not result in amino-acid substitution but can alter gene function and/or alter gene expression. [1] More than 10 million single-nucleotide polymorphisms (SNPs) have been identified in the human genome. [3]
A single genetic variation may play only a moderate or limited role in common diseases, but it may have important interactions with other genetic variations or environmental factors. [4] Most of the genetic research in the oral disease has focused on gene polymorphisms that play a role in the immune response, tissue destructive process, or metabolic mechanism. In some situations, genetic polymorphisms could cause a change in the protein or its expression, possibly resulting in alterations in innate and adaptive immunity and may thus be deterministic in disease progression. On the other hand, genetic polymorphisms may also act like a protector or a destructive factor for a disease. [5] It is thought that SNP analysis will facilitate in identifying multiple genes associated with periodontitis as genetic markers. By acting as genomic markers, SNPs can aid in clarifying risk factors for complex diseases. [1]
Ten to twenty genes may be involved in such complicated multifactorial disease. [2] Recent reports have indicated that allelic variation in cytokine genes and factors regulating their expression may influence the clinical outcome, susceptibility and progression of periodontal disease. Dysregulation of cytokine gene expression may be responsible for the repeated cycles of tissue inflammation observed in these disorders. [6]
Thus, not only gene-gene interactions but also gene-environment interactions form a complex network in which the disease can initiate and progress. Using decision tree analysis, the presence of bacterial species Tannerella forsythia, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and SNPs TNF-857 and interleukin (IL)-1A -889 were identified as discriminators between periodontitis and non-periodontitis. [7]
Some previous studies have shown associations between periodontitis and SNPs in the IL1, IL10, TNF-α and Fc-γ genes. The SNPs in TRAF1 gene was associated with aggressive periodontitis (AgP) and MMP9 gene was associated with chronic periodontitis (CP). Suzuki et al. investigated the associations between 637 SNPs in 244 genes related to systemic diseases and severe periodontitis on a large scale. They reported that SNPs in the GNRH1, PIK3R1, DPP4, FGL2 and CALCR genes are genomic markers for severe periodontitis. [7] Association between periodontitis and specific genotypes such as PECAM-1, MMP-1, BMP-4, human leukocyte antigen (HLA), vitamin D receptors (VDR), N-formyl peptide receptors, vascular endothelial growth factor (VEGF), transforming growth factor (TGF), Alpha-1-antichymotripsin, hydroxy-methyl-glutaryl CoA reductase, interferon-α, resistin-420, β-defensin, C-reactive protein (CRP), calcitonin receptor gene polymorphisms. [3],[8],[9],[10],[11],[12],[13] Several localized AgP loci on chromosomes 1, 4, 6 and 9 have been identified by parametric linkage analysis. [9]
Racial variations
Generally, the allele frequencies of SNPs differ greatly among races. The IL-1β 13953 SNP that was suggested to be associated with the severity of periodontitis in Caucasians and Mongolian population were extremely low in Chinese populations and rarely detected in Japanese periodontitis patients or in healthy subjects. Tumor necrosis factor (TNF)-α -1031/-863 and -857 SNPs are associated with severe adult periodontitis in Japanese populations. [14]
Rare G allele of rs689466 among Chinese patients andrs20417 among Taiwanese population was associated with CP. [15] Disease association of COX-2 rs6681231 in a population of Northwestern European ethnicity, rs 20417 [15] and COX-2-765 polymorphism to be associated with AgP in Taiwanese. [16]
Interleukin, IL-1β13954 was reported to be associated with risks of AgP in Caucasians and Chileans, but was not associated with AgP in Hispanic, Chinese, Greek and Japanese individuals. Based on the literature, AgP was associated with polymorphisms of IL-1B13954, TLR4 (299), FcγRIIa-H131 and NADPH genes in Caucasians; IL-6R, FcαRI324, IL6ST, PTGDS, COL4A1, COL1A1, KRT23 and IL-1RN (VNTR) genes in Japanese; and MMP-1-1607, IL-1A14845, IL-1B-511 and ER-a in Chinese. [16]
Rate of IL-1a (+4845), IL-1b (+3954), and IL-1RN (VNTR) tended to be lower in Japanese than Caucasians, whereas the rate in African-Americans was between the Caucasian and the Japanese data. [6] The IL1 positive genotype has been reported in 30% Caucasian North Europe, 43% Spanish, 35.3% Swiss Caucasian, 38.9% Australian Caucasian, 34.8% New Zealand, 26% Mexican, 44.4% Greek, 34.4% Polish and 1.6% Chinese samples. SNPs at - 889 of IL1A and + 3953 of IL1B was noted in Caucasian-Portuguese population. [5] The - 44 CC genotype of the β-defensin-1 gene (DEFB1 rs1800972) may be associated with susceptibility to chronic periodontitis in Japanese. [10]
Interleukins and TNF
Genetic polymorphism in cytokine genes is regarded as a promising factor in inducing periodontal diseases. [2] The genes for IL-1α, IL-1β and IL-(1RNa) are all located on the long-arm of chromosome 2. [6] The SNPs in the IL10 gene at positions -1087, -819 and -592 from the transcriptional start site, which have been associated with altered synthesis of IL10 in response to inflammatory stimuli. [17]
Increased prevalence of the GG genotype was observed for the IL-6-174 polymorphism and may be more prone to developing periodontitis. [18] Genes that encode IL-6Ra were located on chromosomes 1q21 and 9, although the gene on chromosome 9 was found out to be a pseudo gene. IL6R 148892 A/C polymorphism could act as a risk factor for periodontitis. [19]
Some TNF-α and IL-1β SNPs, TNF-α -308, -238, -1031, -863 and -857, variants of which are observed in a relatively large proportion of Japanese, have been identified, and the variant alleles of these SNPs have been suggested to be related to high TNF-α production. TNF-α -308 SNP have been associated with an eight-fold higher transcriptional activation rate in vitro.[14]
IL-1β 13953, -511, -31 have been identified. IL-1β 13953 SNP is the one most studied with respect to severity of periodontitis and was associated with a four-fold increase in IL-1β production. Therefore, these SNPs could be candidate SNPs associated with the severity of periodontitis. [14] Allele 2 of IL1A and IL1B are associated with severe peri-implantitis and determined the success of dental implants. [5]
IL-8 -251 (A/T) single nucleotide polymorphism affects the function of promoter gene and cases presenting with AA genotype produce and release higher levels of IL-8 compared to individuals with AT or TT genotype but could not correlate with severity of periodontitis. The IL-8 -4073 gene promoter was associated with CP in non-smoker Brazilian subjects and the frequency of the A allele was higher in the disease group. [2]
IL12RB2 SNPs influence the responses of cell-mediated immunity to periodontal pathogens and contribute to periodontal disease susceptibility. [20]
TNFα haplotype combination (c.-308G > A and c.-238G > A) could not be proven to be an independent risk factor in periodontitis in general and CP or in AgP. Accordingly, no influence of TNFα promoter polymorphisms (c.-1031T > C, c.-863C > A, c.-857C > T) on the occurrence of periodontitis was detected in several studies. [21] Genetic background of TNFα could be regarded as a modulator of clinical features of periodontitis in coronary patients. [22]
COX-2
The human COX-2 gene, mapped to chromosome 1q25.2-q25.3. In periodontitis, specific COX-2 expression has been reported in gingival tissues. The SNPs within the COX-2gene have been related to increased susceptibility to inflammatory diseases. Genetic linkage analysis performed at localized AgP (LAP) families showed that LAP was linked to chromosome 1q25, covering the COX-2 gene and it is likely that the − 765C allele is protective for periodontitis. [16]
Complements
Complement component deficiencies and increased cleavage seem to be associated with severe CP. The C5 polymorphisms is associated with increased severity of inflammation and periodontal destruction. The C5 gene is located on chromosome 9q34.1. The SNP rs17611 of the C5 gene was more prevalent in the periodontitis patient group than in periodontitis-free controls and, together with smoking, may be associated with periodontitis among the Hong Kong Chinese population. [23]
FcγR
FcγRs are cell-surface receptors for the constant (Fc) region of IgG antibodies. Three different classes of human FcγR family are currently recognized and they encompass 8 genes namely, CD64, encoded by FcγRIa, Ib and Ic genes; CD32, encoded by FcγRIIa, IIb, and IIc genes; CD16, encoded by FcγRIIIa and IIIb genes. [4] Van der Pol et al., reported that FcγRIIA, FcγRIIB, FcγRIIIA and FcγRIIIB are mapped within 3.5cR on chromosome 1, band q23-24. The FcγRIIB-nt645 + 25A/G could be a susceptibility SNP for periodontitis. The FcγRIIBI232T in patients with periodontitis was associated with an increase in the serum-specific IgG2 level against the outer membrane protein from P. gingivalis. [24] Genetic variations of Fragment Crystallizable Gamma Receptor (FcGR), may modify the transcription and hence expression and biological functions of the corresponding receptor molecule, thereby modifying humoral immune responses and influencing one's susceptibility to periodontitis. [4]
PECAM
Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is encoded by a 75 kb gene that resides at the end of the long arm of chromosome 17. The Arg670Gly polymorphism in this exon has been found to be related to diseases such as ischemic heart diseases, myocardial infarction (MI) and stenosis but no significant association with periodontal disease. [25]
S100A8
The S100A8 protein belongs to the family of calcium-binding S100 proteins. The S100A8 gene is a member of the S100 gene cluster on chromosome1q21. The genes S100A8, S100A9 and S100A12 form a secondary cluster, which is adjacent to the core cluster. It encodes a structural protein of 93 amino acids called S100A8. Many studies have demonstrated that the concentration of S100A8 and/or calprotectin in gingival crevicular fluid correlated with both gingivitis and periodontitis. The SNP rs3795391 does not affect the structure of gene products, but it might cause quantitative differences in gene expression and might affect the susceptibility of AgP. [9]
TLR
Toll-like receptors (TLRs) are key sensors of the innate immune system. The TLR2 gene products were found to be upregulated in inflamed gingival tissue. Genetic association studies on TLR2 hitherto did not identify an association of SNPs with AgP or CP. Case-control association study of eight tag SNP, which spanned 23 kb of the complete coding region of TLR2, as well as the resequencing of exon 3 in 47 AgP cases, was not able to identify statistically significant associations of genetic variants of TLR2 with periodontitis [26] Polymorphisms in genes such as TLR4 and CD14 have been associated with increased risk of Gram-negative infections and increase susceptibility to periodontitis. Asp299Gly TLR4 gene polymorphic form is associated with a decreased risk of AgP but not CP in West European Caucasians. [27]
RANK and OPG
Bone resorption by osteoclasts is one of the main symptoms of periodontal and peri-implant diseases. Osteoclastogenesis is controlled by three members of the TNF and TNF-receptor super family: Receptor activator of nuclear factor-kappa B ligand (RANKL), receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG). The OPG gene is located on chromosome 8q, and is a single-copy gene with five exons. The OPG 950C/T and 1181G/C polymorphisms have been implicated with peri-implantitis but no significant association with chronic periodontitis [8] The RANK/RANKL/OPG regulatory axis is also involved in inflammatory bone destruction induced by pro-inflammatory cytokines such as prostaglandin E2 (PGE2), IL-1b, IL-6, IL-11 and TNF-α. RANK polymorphisms have a minor effect in pathogenesis of AgP. [28]
| Genome Wide Association Studies | | |
Demmer et al., analyzed the whole genome to show the differential gene expression of healthy and diseased periodontal sites. They identified numerous up- or downregulated genes in disease compared to health, including apoptosis, angiogenesis, response to microbes, antigen presentation, regulation of metabolism and signal transduction. [29]
Divaris et al., on their Genome Wide Association Study (GWAS) identified 6 loci associated to CP. The loci of NPY, NCR2 and EMR1 had concordant effect direction in a replication sample. The locus of NUAK1 was associated with smoking and CP, but not seen in healthy controls. There was a lack of overlap of risk loci for the moderate and severe CP. The precision and validity of the genetic SNP estimates will improve with time when higher density imputations, whole genome sequencing and larger GWAS samples are incorporated into the study. [30]
Li et al., did not find any meaningful association between smoking status and ethnicity with CP. They concluded that individuals carrying MMP1-1607 2G allele were associated with overexpression of MMP-1, consequently contributing to more susceptibility to CP. Their meta-analysis suggested that MMP-1 g.-1607dupG contribute to the elevated risk of CP. [31]
Schaefer et al., demonstrated statistically significant associations of rs2891168, rs1333042, rs1333048 and rs496892 in chromosomal region 9p21.3 with localized AgP and even stronger associations with generalized AgP. Ernst et al., have also confirmed this association in their GWAS. The chromosomal locus on 9p21.3, which encodes CDKN2A, CDKN2B and ARF may represent one of the postulated genetic links between coronary heart disease and periodontitis. [32],[33]
Implications
SNPs in introns might affect splicing and/or transcription, and missense SNPs in exons might affect function of its product. Such variations can produce a plethora of diseases from variations in morphology to neoplastic transformation. [34],[35],[36]
As evaluation of the function of SNPs, based only on the nucleotide sequence is still very difficult, further functional analysis of these SNPs is needed to elucidate the molecular mechanism of periodontal disease. [28]
Determining the predisposing genetic factors and specific associated inflammatory biomarkers may help the clinician to choose the most reasonable approach to prevent and control the periodontal condition in patients with high susceptibility of periodontal diseases. [2]
Disease biomarkers in saliva are used as a diagnostic tool to screen oral and systemic health. Identification of the qualitative changes in these biomarkers can help in identifying patients with increased susceptibility, sites with active disease, prediction of future-active sites and to monitor therapeutic outcomes. [3]
| Conclusion | | |
With advances in technology and growth in genetic knowledge, a world-wide database could be prepared in the near future with a summary of various genomic markers and its clinical implications in various types of periodontitis. It can pave the way for prompt diagnosis, screen susceptible individuals and develop new strategies to modulate their treatment plan.
| References | | |
| 1. | Suzuki A, Ji G, Numabe Y, Ishii K, Muramatsu M, Kamoi K. Large-scale investigation of genomic markers for severe periodontitis. Odontology 2004;92:43-7. 
|
| 2. | Khosropanah H, Sarvestani EK, Mahmoodi A, Golshah M. Association of IL-8 (-251 A/T) gene polymorphism with clinical parameters and chronic periodontitis. J Dent (Tehran) 2013;10:312-8.
|
| 3. | Taba M Jr, Souza SL, Mariguela VC. Periodontal disease: A genetic perspective. Braz Oral Res 2012;26:32-8.
|
| 4. | Chai L, Song YQ, Zee KY, Leung WK. SNPs of Fc-gamma receptor genes and chronic periodontitis. J Dent Res 2010;89:705-10.
|
| 5. | Vaz P, Gallas MM, Braga AC, Sampaio-Fernandes JC, FelinoA, Tavares P. IL1 gene polymorphisms and unsuccessful dental implants. Clin Oral Implants Res 2012;23:1404-13.
|
| 6. | Tai H, Endo M, Shimada Y, Gou E, Orima K, Kobayashi T, et al. Association of interleukin-1 receptor antagonist gene polymorphisms with early onset periodontitis in Japanese. J Clin Periodontol 2002;29:882-8.
|
| 7. | Laine ML, Moustakis V, Koumakis L, Potamias G, Loos BG. Modeling susceptibility to periodontitis. J Dent Res 2013;92:45-50.
|
| 8. | Kadkhodazadeh M, Tabari ZA, Ardakani MR, Ebadian AR, Brook A. Analysis of osteoprotegerin (OPG) gene polymorphism in Iranian patients with chronic periodontitis and peri-implantitis. A cross-sectional study. Eur J Oral Implantol 2012;5:381-8.
|
| 9. | Ren XY, Xu L, Meng HX, Zhao HS, Lu RF, Chen ZB, et al. Family-based association analysis of S100A8 genetic polymorphisms with aggressive periodontitis. J Periodontal Res 2009;44:184-92.
|
| 10. | Ikuta T, Inagaki Y, Tanaka K, Saito T, Nakajima Y, Bando M, et al. Gene polymorphism of β-defensin-1 is associated with susceptibility to periodontitis in Japanese. Odontology 2013.
|
| 11. | Ianni M, Bruzzesi G, Pugliese D, Porcellini E, Carbone I, Schiavone A, et al. Variations in inflammatory genes are associated with periodontitis. Immun Ageing 2013;10:39.
|
| 12. | Patel SP, Raju PA. Resistin in serum and gingival crevicular fluid as a marker of periodontal inflammation and its correlation with single-nucleotide polymorphism in human resistin gene at -420. Contemp Clin Dent 2013;4:192-7.
[PUBMED]  |
| 13. | Tian Y, Li JL, Hao L, Yue Y, Wang M, Loo WT, et al. Association of cytokines, high sensitive C-reactive protein, VEGF and beta-defensin-1 gene polymorphisms and their protein expressions with chronic periodontitis in the Chinese population. Int J Biol Markers 2013;28:100-7.
|
| 14. | Soga Y, Nishimura F, Ohyama H, Maeda H, Takashiba S, Murayama Y. Tumor necrosis factor-alpha gene (TNF-α) -1031/-863, -857 single-nucleotide polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese. J Clin Periodontol 2003;30:524-31.
|
| 15. | Schaefer AS, Richter GM, Nothnagel M, Laine ML, Noack B, Glas J, et al. COX-2 is associated with periodontitis in Europeans. J Dent Res 2010;89:384-8.
|
| 16. | Ho YP, Lin YC, Yang YH, Ho KY, Wu YM, Tsai CC. Cyclooxygenase-2 Gene-765single nucleotide polymorphism as a protective factor against periodontitis in Taiwanese. J Clin Periodontol 2008;35:1-8.
|
| 17. | Scarel-Caminaga RM, Trevilatto PC, Souza AP, Brito RB, Camargo LE, Line SR. Interleukin 10 gene promoter polymorphisms are associated with chronic periodontitis. J Clin Periodontol 2004;31:443-8.
|
| 18. | Franch-Chillida F, Nibali L, Madden I, Donos N, Brett P. Association between interleukin-6 polymorphisms and periodontitis in Indian non-smokers. J Clin Periodontol 2010;37:137-44.
|
| 19. | Galicia JC, Tai H, Komatsu Y, Shimada Y, Ikezawa I, Yoshie H. Interleukin-6 receptor gene polymorphisms and periodontitis in a non-smoking Japanese population. J Clin Periodontol 2006;33:704-9.
|
| 20. | Takeuchi-Hatanaka K, Ohyama H, Nishimura F, Kato-Kogoe N, Soga Y, Matsushita S, et al. Polymorphisms in the 5` flanking region of IL12RB2 are associated with susceptibility to periodontal diseases in the Japanese population. J Clin Periodontol 2008;35:317-23.
|
| 21. | Schulz S, Machulla HK, Altermann W, Klapproth J, Zimmermann U, Glaser C, et al. Genetic markers of tumor necrosis factor alpha in aggressive and chronic periodontitis. J Clin Periodontol 2008;35:493-500.
|
| 22. | Schulz S, Schlitt A, Lutze A, Lischewski S, Seifert T, Dudakliewa T, et al. The importance of genetic variants in TNFα for periodontal disease in a cohort of coronary patients. J Clin Periodontol 2012;39:699-706.
|
| 23. | Chai L, Song YQ, Zee KY, Leung WK. Single nucleotide polymorphisms of complement component 5 and periodontitis. J Periodont Res 2010;45:301-8.
|
| 24. | Iwanaga R, Sugita N, Hirano E, Sasahara J, Kikuchi A, Tanaka K, et al. FcγRIIB polymorphisms, periodontitis and preterm birth in Japanese pregnant women. J Periodont Res 2011;46:292-302.
|
| 25. | Kdkhodazadeh M, Hajilooi M, Houshmand B, Khazaei S, Gholami L, Alijani S. Evaluation of PECAM-1 gene polymorphism in patients with periodontal disease and healthy individuals. ISRN Dent 2012;2014:751920.
|
| 26. | Richter GM, Graetz C, Pohler P, Nothnagel M, Dommisch H, Laine ML, et al. Common genetic risk variants of TLR2 are not associated with periodontitis in large European case-control populations. J Clin Periodontol 2012;39:315-22.
|
| 27. | James JA, Poulton KV, Haworth SE, Payne D, McKay IJ, Clarke FM, et al. Polymorphisms of TLR4 but not CD14 are associated with a decreased risk of aggressive periodontitis. J Clin Periodontol 2007;34:111-7.
|
| 28. | Soedarsono N, Rabello D, Kamei H, Fuma D, Ishihara Y, Suzuki M, et al. Evaluation of RANK/RANKL/OPG gene polymorphisms in aggressive periodontitis. J Periodont Res 2006;41:397-404.
|
| 29. | Demmer RT, Behle JH, Wolf DL, Handfield M, Kebschull M, Celenti R, et al. Transcriptomes in healthy and diseased gingival tissues. J Periodontol 2008;79:2112-24.
|
| 30. | Divaris K, Monda KL, North KE, Olshan AF, Reynolds LM, Hsueh WC, et al. Exploring the genetic basis of chronic periodontitis: A genome-wide association study. Hum Mol Genet 2013;22:2312-24.
|
| 31. | Li D, Cai Q, Ma L, Wang M, Ma J, Zhang W, et al. Association between MMP-1 g.-1607dupG polymorphism and periodontitis susceptibility: A meta-analysis. PLoS One 2013;8:e59513.
|
| 32. | Ernst FD, Uhr K, Teumer A, Fanghanel J, Schulz S, Noack B, et al. Replication of the association of chromosomal region 9p21.3 with generalized aggressive periodontitis (gAgP) using an independent case-control cohort. BMC Med Genet 2010;11:119.
|
| 33. | Murugan M, Ramalingam K, Nazzuredin M, Rashed HA, Punamalai G. SNP's and its correlation with hypertension: A comprehensive review. Dent Med Res 2013;1:3-6.
|
| 34. | Ramalingam K, Gajula P. Mandibular Talon cusp: A rare presentation with literature review. J Nat Sci Biol Med 2011;2:225-8.
|
| 35. | Jeyanthi K, Ramalingam K, Sherlin HJ, Anuja N, Ramani P, Priya P, et al. Pleomorphic adenoma in the infra-temporal space: The first case report. Head Neck Pathol 2007;1:173-7.
|
| 36. | Goel R, Ramalingam K, Ramani P, Chandrasekar T. Sino nasal undifferentiated carcinoma: A rare entity. J Nat Sci Biol Med 2012;3:101-4.
|
| This article has been cited by | | 1 |
DEFB1, MMP9 AND COX2 GENE POLYMORPHISMS AND PERIODONTITIS |
|
| O. V. Dienha, V. B. Pyndus, K. V. Litovkin, S. A. Shnaider, P. Džupa, V. M. Pochtar, O. V. Suslova | | World of Medicine and Biology. 2023; 19(83): 53 | | [Pubmed] | [DOI] | | | 2 |
Proinflammatory Cytokine Polymorphisms and Severity of Periodontitis in a Cohort of Bulgarian Patients |
|
| Z. Pashova-Tasseva, Ch. Popova, E. Tosheva, A. Mlachkova | | Acta Medica Bulgarica. 2022; 49(4): 31 | | [Pubmed] | [DOI] | | | 3 |
Association of vitamin D binding protein and vitamin D receptor gene polymorphisms in Iranian patients with chronic periodontitis |
|
| Bahareh Nazemisalman,Surena Vahabi,Ehsan Sabouri,Sepanta Hosseinpour,Sara Doaju | | Odontology. 2018; | | [Pubmed] | [DOI] | | | 4 |
Genetic polymorphisms of TNFA and IL-1A and generalized aggressive periodontitis |
|
| BARNEA, TEODORA VIRGINIA, ANCA SAVA, CARMEN GENTIMIR, ANCUŢA GORIUC, OTILIA BOIŞTEANU, LILIANA CHELARU, ROXANA IRINA IANCU et al | | Rom J Morphol Embryol. 2015; 56(2): 459-464 | | [Pubmed] | [PDF] | | | 5 |
ASSOCIATION OF CALCITONIN RECEPTOR 1340 C> T POLYMORPHISM WITH PERIODONTITIS SUSCEPTIBILITY." |
|
| Sunitha, T., et al. | | IJABFP. 2015; 6(2) | | [Pubmed] | [PDF] | | | 6 |
The Genome, the microbiome, and the human epigenome. A contemporary view of the ecological triad. |
|
| Agustín Zerón | | Revista ADM. 2014; 71(4): 162-170 | | [Pubmed] | [PDF] | |
|
 |
|
|
|
Search Pubmed for