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Dyslipidemia rather than Type 2 Diabetes Mellitus or Chronic Periodontitis Affects the Systemic Expression of Pro- and Anti-Inflammatory Genes.

ABSTRACT: A high percentage of type 2 diabetes mellitus (T2D) patients are also affected by dyslipidemia and chronic periodontitis (CP), but no studies have determined the gene expression in patients that are simultaneously affected by all three diseases. We investigated the systemic expression of immune-related genes in T2D, dyslipidemia, and CP patients. One hundred and fifty patients were separated into five groups containing 30 individuals each: (G1) poorly controlled T2D with dyslipidemia and CP; (G2) well-controlled T2D with dyslipidemia and CP; (G3) normoglycemic individuals with dyslipidemia and CP; (G4) healthy individuals with CP; (G5) systemic and periodontally healthy individuals. Blood analyses of lipid and glycemic profiles were carried out. The expression of genes, including IL10, JAK1, STAT3, SOCS3, IP10, ICAM1, IFNA, IFNG, STAT1, and IRF1, was investigated by RT-qPCR. Patients with dyslipidemia demonstrated statistically higher expression of the IL10 and IFNA genes, while IFNG, IP10, IRF1, JAK1, and STAT3 were lower in comparison with nondyslipidemic patients. Anti-inflammatory genes, such as IL10, positively correlated with parameters of glucose, lipid, and periodontal profiles, while proinflammatory genes, such as IFNG, were negatively correlated with these parameters. We conclude that dyslipidemia appears to be the primary disease that is associated with gene expression of immune-related genes, while parameters of T2D and CP were correlated with the expression of these important immune genes.

SUBMITTER: Nepomuceno R

PROVIDER: S-EPMC5337859 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Dyslipidemia rather than Type 2 Diabetes Mellitus or Chronic Periodontitis Affects the Systemic Expression of Pro- and Anti-Inflammatory Genes.

Nepomuceno Rafael R Villela Bárbara Scoralick BS Corbi Sâmia Cruz Tfaile SC Bastos Alliny De Souza AS Dos Santos Raquel Alves RA Takahashi Catarina Satie CS Orrico Silvana Regina Perez SR Scarel-Caminaga Raquel Mantuaneli RM

Mediators of inflammation 20170220

A high percentage of type 2 diabetes mellitus (T2D) patients are also affected by dyslipidemia and chronic periodontitis (CP), but no studies have determined the gene expression in patients that are simultaneously affected by all three diseases. We investigated the systemic expression of immune-related genes in T2D, dyslipidemia, and CP patients. One hundred and fifty patients were separated into five groups containing 30 individuals each: (G1) poorly controlled T2D with dyslipidemia and CP; (G2 ...[more]

PMID: 28316372

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Project description:Type 2 diabetes mellitus (T2DM), dyslipidemia and periodontitis are frequently associated pathologies; however, there are no studies showing the peripheral blood transcript profile of these combined diseases. Here we identified the differentially expressed genes (DEGs) of circulating lymphocytes and monocytes to reveal potential biomarkers that may be used as molecular targets for future diagnosis of each combination of these pathologies (compared to healthy patients) and give insights into the underlying molecular mechanisms of these diseases. Study participants (n = 150) were divided into groups: (H) systemically and periodontal healthy (control group); (P) with periodontitis, but systemically healthy; (DL-P) with dyslipidemia and periodontitis; (T2DMwell-DL-P) well-controlled type 2 diabetes mellitus with dyslipidemia and periodontitis; and (T2DMpoorly-DL-P) poorly-controlled type 2 diabetes mellitus with dyslipidemia and periodontitis. We preprocessed the microarray data using the Robust Multichip Average (RMA) strategy, followed by the RankProd method to identify candidates for DEGs. Furthermore, we performed functional enrichment analysis using Ingenuity Pathway Analysis and Gene Set Enrichment Analysis. DEGs were submitted to pairwise comparisons, and selected DEGs were validated by quantitative polymerase chain reaction. Validated DEGs verified from T2DMpoorly-DL-P versus H were: TGFB1I1, VNN1, HLADRB4 and CXCL8; T2DMwell-DL-P versus H: FN1, BPTF and PDE3B; DL-P versus H: DAB2, CD47 and HLADRB4; P versus H: IGHDL-P, ITGB2 and HLADRB4. In conclusion, we identified that circulating lymphocytes and monocytes of individuals simultaneously affected by T2DM, dyslipidemia and periodontitis, showed an altered molecular profile mainly associated to inflammatory response, immune cell trafficking, and infectious disease pathways. Altogether, these results shed light on novel potential targets for future diagnosis, monitoring or development of targeted therapies for patients sharing these conditions.

Project description:Background and objectiveIn recent years, the complex interplay between systemic health and oral well-being has emerged as a focal point for researchers and healthcare practitioners. Among the several important connections, the convergence of Type 2 Diabetes Mellitus (T2DM), dyslipidemia, chronic periodontitis, and peripheral blood mononuclear cells (PBMCs) is a remarkable example. These components collectively contribute to a network of interactions that extends beyond their domains, underscoring the intricate nature of human health. In the current study, bioinformatics analysis was utilized to predict the interactomic hub genes involved in type 2 diabetes mellitus (T2DM), dyslipidemia, and periodontitis and their relationships to peripheral blood mononuclear cells (PBMC) by machine learning algorithms.Materials and methodsGene Expression Omnibus datasets were utilized to identify the genes linked to type 2 diabetes mellitus(T2DM), dyslipidemia, and Periodontitis (GSE156993).Gene Ontology (G.O.) Enrichr, Genemania, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used for analysis for identification and functionalities of hub genes. The expression of hub D.E.G.s was confirmed, and an orange machine learning tool was used to predict the hub genes.ResultThe decision tree, AdaBoost, and Random Forest had an A.U.C. of 0.982, 1.000, and 0.991 in the R.O.C. curve. The AdaBoost model showed an accuracy of (1.000). The findings imply that the AdaBoost model showed a good predictive value and may support the clinical evaluation and assist in accurately detecting periodontitis associated with T2DM and dyslipidemia. Moreover, the genes with p-value < 0.05 and A.U.C.>0.90, which showed excellent predictive value, were thus considered hub genes.ConclusionThe hub genes and the D.E.G.s identified in the present study contribute immensely to the fundamentals of the molecular mechanisms occurring in the PBMC associated with the progression of periodontitis in the presence of T2DM and dyslipidemia. They may be considered potential biomarkers and offer novel therapeutic strategies for chronic inflammatory diseases.

Dataset Information

Dyslipidemia rather than Type 2 Diabetes Mellitus or Chronic Periodontitis Affects the Systemic Expression of Pro- and Anti-Inflammatory Genes.

Publications

Dyslipidemia rather than Type 2 Diabetes Mellitus or Chronic Periodontitis Affects the Systemic Expression of Pro- and Anti-Inflammatory Genes.

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