Investigação da expressão de genes do metabolismo lipídico em pacientes com Diabetes Mellitus tipo 2, Dislipidemia e Doença Periodontal Crônica
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Data
2016-03-22
Autores
Silva, Romerito Lins da [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O Diabetes Mellitus tipo 2 (DM2) e a Dislipidemia são doenças metabólicas que podem induzir a progressão de doenças coexistentes com patogênese inflamatória semelhante, como a doença periodontal (DP). Adipocinas são proteínas produzidas pelo tecido adiposo que possuem atividade metabólica, podendo influenciar o estado hiperinflamatório do hospedeiro. O objetivo deste estudo foi investigar a influência do DM2 (metabolicamente compensado ou descompensado), Dislipidemia e DP crônica, na expressão de genes relacionados à adipocinas em células mononucleares do sangue periférico (PBMC) e buscar correlacionar a expressão desses genes com o perfil clínico periodontal, glicêmico e lipídico. Investigaram-se cinco grupos de pacientes (30 indivíduos cada): G1 (diabetes descompensado, dislipidemia e doença periodontal), G2 (diabetes compensado, dislipidemia e doença periodontal), G3 (dislipidemia e doença periodontal), G4 (apenas doença periodontal) e G5(sistemicamente e periodontalmente saudável). Os pacientes foram submetidos a exame periodontal completo e avaliação bioquímica dos perfis glicêmico e lipídico. Foi extraído RNA do sangue de cada paciente para investigação da expressão dos genes Adiponectina (ADIPOQ), Receptor 1 da Adiponectina (ADIPOR1), Leptina (LEP) e Resistina (RETN) por meio da Transcriptase Reversa seguida de Reação em Cadeia da Polimerase quantitativa em tempo real (RT-qPCR). Para a expressão gênica realizou-se o teste de Kruskal-Wallis, seguido pelo pós-teste de Dunn. Nas correlações entre os parâmetros clínicos, bioquímicos e de expressão gênica utilizou-se o coeficiente de correlação de Pearson (dados paramétricos) ou Spearman (dados não paramétricos). O estado de descompensação metabólica do DM2 pareceu estar associado à maior expressão do gene LEP no grupo G1(DM2 descompensado) comparando-se com o grupo G2 (DM2 compensado), G4 e G5 (não dislipidêmicos). Expressão significativamente maior do gene RETN foi observada no grupo Controle comparando-se aos grupos com DM2, independentemente do nível de descompensação metabólica. A expressão dos genes investigados correlacionou-se significativamente com alguns parâmetros glicêmicos e lipídicos, mas não com os físicos. Os níveis de expressão dos genes ADIPOR1, LEP e RETN pareceram ser influenciados pela DP crônica, com correlação positiva com parâmetros clínicos indicativos de saúde periodontal e negativa com parâmetros indicativos de doença ativa. Conclui-se que não houve diferença entre os grupos para a expressão do gene ADIPOR1, no entanto, a modulação de expressão dos genes RETN e LEP variou para os diferentes grupos, especialmente nos indivíduos com DM2. Houve correlação dos genes ADIPOR1, LEP e RETN com parâmetros glicêmicos, lipídicos e de saúde periodontal nos indivíduos estudados.
Type 2 Diabetes Mellitus (T2D) and dyslipidemia are metabolic diseases that can induce the progression of coexisting inflammatory injury and they have similar pathogenesis to chronic periodontitis (CP). Adipokines are proteins produced by fat tissue that have metabolic activity and can influence the host hyper-inflammatory state. The aim of this study was to investigate in poorly or well-controlled T2D and normoglycemic individuals, both conditions associated with dyslipidemia and CP, the systemic expression of adipokines genes and its correlation with glycemic, lipid and periodontal profiles. One hundred fifty patients were separated into groups (G) of 30 subjects each: (G1) poorly controlled T2D with dyslipidemia and CP; (G2) wellcontrolled T2D with dyslipidemia and CP; (G3) normoglycemic individuals with dyslipidemia and CP; (G4) individuals with CP; (G5) systemic and periodontal healthy individuals (control). All patients underwent physical and periodontal examination and biochemical evaluation of glycemic and lipid profiles. Total RNA was extracted from peripheral blood mononuclear cells (PBMC) of patients for gene expression investigation of: Adiponectin (ADIPOQ), Adiponectin Receptor 1 (ADIPOR1), Leptin (LEP) and Resistin (RETN) by Reverse Transcriptase followed by real-time quantitative Polymerase Chain Reaction (RT-qPCR). Gene expression was evaluated by Kruskal- Wallis test followed by Dunn's post-test. Correlations among clinical, biochemical and gene expressions were investigated by Pearson correlation coefficient (parametric data) or Spearman (nonparametric data). The poor control of T2D seems to be associated with increased expression of the LEP in G1 (G1) compared with G2 (well-controlled T2D), G4 and G5 (not dyslipidemics). Significant higher expression of the RETN gene was observed in the Control group in comparison to the groups of T2D patients, independently of the glycemic control. The expression levels of the investigated genes were significantly correlated with some glycemic and lipid parameters, but not with physical parameters. The expression of the ADIPOR1, LEP e RETN genes seemed to be influenced by CP with a positive correlation between clinical parameters that are indicative of periodontal health and negative correlation with active disease parameters In conclusion, there was no difference among groups for the expression of the ADIPOR1 gene; however, the expression modulation of RETN and LEP genes varied among the different groups, especially in individuals with T2D. There were correlat ion of ADIPOR1, LEP and RETN genes with glycemic, lipid and periodontal health parameters in the studied subjects.
Type 2 Diabetes Mellitus (T2D) and dyslipidemia are metabolic diseases that can induce the progression of coexisting inflammatory injury and they have similar pathogenesis to chronic periodontitis (CP). Adipokines are proteins produced by fat tissue that have metabolic activity and can influence the host hyper-inflammatory state. The aim of this study was to investigate in poorly or well-controlled T2D and normoglycemic individuals, both conditions associated with dyslipidemia and CP, the systemic expression of adipokines genes and its correlation with glycemic, lipid and periodontal profiles. One hundred fifty patients were separated into groups (G) of 30 subjects each: (G1) poorly controlled T2D with dyslipidemia and CP; (G2) wellcontrolled T2D with dyslipidemia and CP; (G3) normoglycemic individuals with dyslipidemia and CP; (G4) individuals with CP; (G5) systemic and periodontal healthy individuals (control). All patients underwent physical and periodontal examination and biochemical evaluation of glycemic and lipid profiles. Total RNA was extracted from peripheral blood mononuclear cells (PBMC) of patients for gene expression investigation of: Adiponectin (ADIPOQ), Adiponectin Receptor 1 (ADIPOR1), Leptin (LEP) and Resistin (RETN) by Reverse Transcriptase followed by real-time quantitative Polymerase Chain Reaction (RT-qPCR). Gene expression was evaluated by Kruskal- Wallis test followed by Dunn's post-test. Correlations among clinical, biochemical and gene expressions were investigated by Pearson correlation coefficient (parametric data) or Spearman (nonparametric data). The poor control of T2D seems to be associated with increased expression of the LEP in G1 (G1) compared with G2 (well-controlled T2D), G4 and G5 (not dyslipidemics). Significant higher expression of the RETN gene was observed in the Control group in comparison to the groups of T2D patients, independently of the glycemic control. The expression levels of the investigated genes were significantly correlated with some glycemic and lipid parameters, but not with physical parameters. The expression of the ADIPOR1, LEP e RETN genes seemed to be influenced by CP with a positive correlation between clinical parameters that are indicative of periodontal health and negative correlation with active disease parameters In conclusion, there was no difference among groups for the expression of the ADIPOR1 gene; however, the expression modulation of RETN and LEP genes varied among the different groups, especially in individuals with T2D. There were correlat ion of ADIPOR1, LEP and RETN genes with glycemic, lipid and periodontal health parameters in the studied subjects.
Descrição
Palavras-chave
Diabetes mellitus tipo 2, Doenças periodontais, Dislipidemias, Expressão gênica, Adipocinas, Type 2 diabetes mellitus, Periodontal diseases, Dyslipidemias, Gene expression, Adipokines