Genome-Wide Analysis of Periodontal and Peri-Implant Cells and Tissues

Kebschull, Moritz; Hülsmann, Claudia; Hoffmann, Per; Papapanou, Panos N.

doi:10.1007/978-1-4939-6685-1_18

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…Microarray analysis of mRNA expression is a powerful tool to elucidate screening profiles and is capable of efficiently narrowing down candidate genes associated with multifactorial diseases and investigating underlying mechanisms of diseases and biomarkers for diagnosis and prognosis [4–9, 32, 33]. Furthermore, the clinical application of biomarkers at an early stage is important for global health [32].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Investigation of molecular biomarker candidates for diagnosis and prognosis of chronic periodontitis by bioinformatics analysis of pooled microarray gene expression datasets in Gene Expression Omnibus (GEO)

2019

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Background Chronic periodontitis (CP) is a multifactorial inflammatory disease. For the diagnosis of CP, it is necessary to investigate molecular biomarkers and the biological pathway of CP. Although analysis of mRNA expression profiling with microarray is useful to elucidate pathological mechanisms of multifactorial diseases, it is expensive. Therefore, we utilized pooled microarray gene expression data on the basis of data sharing to reduce hybridization costs and compensate for insufficient mRNA sampling. The aim of the present study was to identify molecular biomarker candidates and biological pathways of CP using pooled datasets in the Gene Expression Omnibus (GEO) database. Methods Three pooled transcriptomic datasets (GSE10334, GSE16134, and GSE23586) of gingival tissue with CP in the GEO database were analyzed for differentially expressed genes (DEGs) using GEO2R, functional analysis and biological pathways with the Database of Annotation Visualization and Integrated Discovery database, Protein-Protein Interaction (PPI) network and hub gene with the Search Tool for the Retrieval of Interaction Genes database, and biomarker candidates for diagnosis and prognosis and upstream regulators of dominant biomarker candidates with the Ingenuity Pathway Analysis database. Results We shared pooled microarray datasets in the GEO database. One hundred and twenty-three common DEGs were found in gingival tissue with CP, including 81 upregulated genes and 42 downregulated genes. Upregulated genes in Gene Ontology were significantly enriched in immune responses, and those in the Kyoto Encyclopedia of Genes and Genomes pathway were significantly enriched in the cytokine-cytokine receptor interaction pathway, cell adhesion molecules, and hematopoietic cell lineage. From the PPI network, the 12 nodes with the highest degree were screened as hub genes. Additionally, six biomarker candidates for CP diagnosis and prognosis were screened. Conclusions We identified several potential biomarkers for CP diagnosis and prognosis (e.g., CSF3, CXCL12 , IL1B , MS4A1 , PECAM1 , and TAGLN ) and upstream regulators of biomarker candidates for CP diagnosis ( TNF and TGF2 ). We also confirmed key genes of CP pathogenesis such as CD19 , IL8 , CD79A , FCGR3B , SELL , CSF3 , IL1B , FCGR2B , CXCL12 , C3 , CD53 , and IL10RA . To our knowledge, this is the first report to reveal associations of CD53 , ...

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Investigation of molecular biomarker candidates for diagnosis and prognosis of chronic periodontitis by bioinformatics analysis of pooled microarray gene expression datasets in Gene Expression Omnibus (GEO)

2019

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“…Finally, a recent genome-wide association study of lipopolysaccharide-induced periodontitis in mice identified CXCR3 as a susceptibility locus for bone loss in that model. 47 Other notable investigations have used genotyping arrays with exome content, 48 whole-exome sequencing, 49,50 RNA expression/ multi-omics profiling, 51,52 and several post hoc bioinformatics and machine learning classification approaches 53,54 to study the molecular and genomic basis of periodontitis. The study of gene expression and other more functional approaches (as opposed to genetic association studies) is a key complement to genome-wide association studies.…”

Section: Periodontal Diseasementioning

confidence: 99%

Genomics of periodontal disease and tooth morbidity

Morelli

Agler

Divaris

2019

Periodontology 2000

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In this review we critically summarize the evidence base and the progress to date regarding the genomic basis of periodontal disease and tooth morbidity (ie, dental caries and tooth loss), and discuss future applications and research directions in the context of precision oral health and care. Evidence for these oral/dental traits from genome‐wide association studies first emerged less than a decade ago. Basic and translational research activities in this domain are now under way by multiple groups around the world. Key departure points in the oral health genomics discourse are: (a) some heritable variation exists for periodontal and dental diseases; (b) the environmental component (eg, social determinants of health and behavioral risk factors) has a major influence on the population distribution but probably interacts with factors of innate susceptibility at the person‐level; (c) sizeable, multi‐ethnic, well‐characterized samples or cohorts with high‐quality measures on oral health outcomes and genomics information are required to make decisive discoveries; (d) challenges remain in the measurement of oral health and disease, with current periodontitis and dental caries traits capturing only a part of the health‐disease continuum, and are little or not informed by the underlying biology; (e) the substantial individual heterogeneity that exists in the clinical presentation and lifetime trajectory of oral disease can be identified and leveraged in a precision medicine framework or, if unappreciated, can hamper translational efforts. In this review we discuss how composite or biologically informed traits may offer improvements over clinically defined ones for the genomic interrogation of oral diseases. We demonstrate the utility of the results of genome‐wide association studies for the development and testing of a genetic risk score for severe periodontitis. We conclude that exciting opportunities lie ahead for improvements in the oral health of individual patients and populations via advances in our understanding of the genomic basis of oral health and disease. The pace of new discoveries and their equitable translation to practice will largely depend on investments in the education and training of the oral health care workforce, basic and population research, and sustained collaborative efforts..

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“…Considerable effort has occurred in attempting to define various genetic influences on the population-based extent and severity of the disease [13,14,15,16]. These studies have identified some unique subpopulations with clearly altered host functions that increase susceptibility, based on various single nucleotide polymorphisms (SNP) or mutations including genes controlling the production of inflammatory mediators and tissue and bone regulatory molecules [17,18,19,20,21,22], as well as some genome-wide association studies (GWAS) that have attempted to identify gene(s) that confer risk for disease [14,19,23,24,25]. More recent reports have also described epigenetic alterations in the genomes of periodontitis patients [26,27,28,29,30,31,32].…”

Section: Introductionmentioning

confidence: 99%

Serum Nutrient Levels and Aging Effects on Periodontitis

et al. 2018

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Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults >30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. Moderate/severe disease patients had lower cis-β-carotene levels across all racial/ethnic groups and these decreased levels in moderate/severe periodontitis were exacerbated with age. β-cryptoxanthin demonstrated lower levels in severe disease patients across the entire age range in all racial/ethnic groups. Folate differences were evident across the various age groups with consistently lower levels in periodontitis patients >30 years and most pronounced in females. Lower levels of vitamin D were consistently noted across the entire age range of patients with a greater difference seen in females with periodontitis. Finally, an analytical approach to identify interactions among these nutrients related to age and periodontitis showed interactions of vitamin D in females, and folate with race in the population. These findings suggest that improving specific nutrient intake leading to elevated blood levels of a combination of these protective factors may provide a novel strategy to affect the significant increase in periodontitis that occurs with aging.

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Genome-Wide Analysis of Periodontal and Peri-Implant Cells and Tissues

Cited by 4 publications

References 22 publications

RETRACTED ARTICLE: Investigation of molecular biomarker candidates for diagnosis and prognosis of chronic periodontitis by bioinformatics analysis of pooled microarray gene expression datasets in Gene Expression Omnibus (GEO)

RETRACTED ARTICLE: Investigation of molecular biomarker candidates for diagnosis and prognosis of chronic periodontitis by bioinformatics analysis of pooled microarray gene expression datasets in Gene Expression Omnibus (GEO)

Genomics of periodontal disease and tooth morbidity

Serum Nutrient Levels and Aging Effects on Periodontitis

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