PMID- 32424199 OWN - NLM STAT- MEDLINE DCOM- 20201204 LR - 20210518 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 May 18 TI - Circulating lymphocytes and monocytes transcriptomic analysis of patients with type 2 diabetes mellitus, dyslipidemia and periodontitis. PG - 8145 LID - 10.1038/s41598-020-65042-9 [doi] LID - 8145 AB - 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. FAU - Corbi, Samia C T AU - Corbi SCT AD - Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP- Sao Paulo State University, Araraquara, 14801385, SP, Brazil. AD - Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, UNESP- Sao Paulo State University, Araraquara, 14801385, SP, Brazil. FAU - de Vasconcellos, Jaira F AU - de Vasconcellos JF AD - Molecular Genomics and Therapeutics Section, Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Building 10, Room 9D11, Bethesda, MD, 20892, USA. AD - Department of Surgery, Uniformed Services University of the Health Sciences and Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. FAU - Bastos, Alliny S AU - Bastos AS AD - Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP- Sao Paulo State University, Araraquara, 14801385, SP, Brazil. FAU - Bussaneli, Diego Girotto AU - Bussaneli DG AUID- ORCID: 0000-0001-9078-7385 AD - Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, UNESP- Sao Paulo State University, Araraquara, 14801385, SP, Brazil. FAU - da Silva, Barbara Roque AU - da Silva BR AD - Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, UNESP- Sao Paulo State University, Araraquara, 14801385, SP, Brazil. FAU - Santos, Raquel Alves AU - Santos RA AD - Postgraduate Program in Sciences of the University of Franca, Franca, 14404600, SP, Brazil. FAU - Takahashi, Catarina S AU - Takahashi CS AD - Department of Genetics, Faculty of Medicine of Ribeirao Preto, USP - University of Sao Paulo, Ribeirao Preto, 14049900, SP, Brazil. AD - Department of Biology, Faculty of Philosophy Sciences and Letters of Ribeirao Preto, USP -University of Sao Paulo, Ribeirao Preto, 14049900, SP, Brazil. FAU - de S Rocha, Cristiane AU - de S Rocha C AUID- ORCID: 0000-0001-5678-2070 AD - Department of Medical Genetics and Medicine Genomics, University of Campinas - UNICAMP, Campinas, 13083-887, SP, Brazil. FAU - Carvalho, Benilton de Sa AU - Carvalho BS AD - Department of Statistics, Institute of Mathematics, Statistics and Scientific Computing, University of Campinas, 13083-859, Sao Paulo, Brazil. FAU - Maurer-Morelli, Claudia V AU - Maurer-Morelli CV AD - Department of Medical Genetics and Medicine Genomics, University of Campinas - UNICAMP, Campinas, 13083-887, SP, Brazil. FAU - Orrico, Silvana R P AU - Orrico SRP AD - Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP- Sao Paulo State University, Araraquara, 14801385, SP, Brazil. AD - Advanced Research Center in Medicine, Union of the Colleges of the Great Lakes (UNILAGO), Sao Jose do Rio Preto, SP, 15030-070, Brazil. FAU - Barros, Silvana P AU - Barros SP AD - Department of Periodontology, University of North Carolina at Chapel Hill - UNC, School of Dentistry, Chapel Hill, NC, USA. FAU - Scarel-Caminaga, Raquel M AU - Scarel-Caminaga RM AD - Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, UNESP- Sao Paulo State University, Araraquara, 14801385, SP, Brazil. raquel.caminaga@unesp.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200518 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 SB - IM MH - Adult MH - Chronic Periodontitis/complications/*genetics/metabolism MH - Diabetes Mellitus, Type 2/complications/*genetics/metabolism MH - Dyslipidemias/complications/*genetics/metabolism MH - Female MH - Gene Expression Profiling MH - Humans MH - Lymphocytes/*metabolism MH - Male MH - Middle Aged MH - Monocytes/*metabolism MH - Transcriptome PMC - PMC7235087 COIS- The authors declare no competing interests. EDAT- 2020/05/20 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/05/18 CRDT- 2020/05/20 06:00 PHST- 2019/09/01 00:00 [received] PHST- 2020/04/21 00:00 [accepted] PHST- 2020/05/20 06:00 [entrez] PHST- 2020/05/20 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/05/18 00:00 [pmc-release] AID - 10.1038/s41598-020-65042-9 [pii] AID - 65042 [pii] AID - 10.1038/s41598-020-65042-9 [doi] PST - epublish SO - Sci Rep. 2020 May 18;10(1):8145. doi: 10.1038/s41598-020-65042-9.