RESUMO
OBJECTIVES: To explore the proteomic changes in thyroid tissue from GD patients and find new biomarkers for the prevention, diagnosis as well as the treatment of GD. DESIGN AND METHODS: Group1 included five thyroid specimens of GD cases and 5 normal thyroid tissue samples which were removed surgically and collected. The proteins were extracted from these thyroid tissues and then the differentially expressed protein spots were identified by MALDI-TOF-MS. The interested proteins were further validated in more specimens (group2: 11 pathological thyroid specimens and 7 normal thyroid tissue samples). RESULTS: A total of 34 differentially expressed proteins were observed, and the majority of these proteins were involved in endoplasmic reticulum stress (ER-stress), oxidative stress, energy metabolism, cytoskeleton and movement. The overexpression of calreticulin(CALR) and heat shock 70kDa protein 5(HSPA5) was further validated. CONCLUSION: Alltogether, abundant new candidate molecules, especially proteins related to ER-stress, were found to be involved in the pathogenesis of GD.
Assuntos
Calreticulina/metabolismo , Doença de Graves/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteômica , Glândula Tireoide/metabolismo , Adulto , Chaperona BiP do Retículo Endoplasmático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Glândula Tireoide/patologia , Adulto JovemRESUMO
The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves' disease (GD) patients, 353 Hashimoto's thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD.
Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Epistasia Genética , Doença de Graves/genética , Tireoidite Autoimune/genética , Adulto , Estudos de Casos e Controles , DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , DNA Metiltransferase 3A , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , DNA Metiltransferase 3BRESUMO
The objective of this study was to investigate histone modification patterns in peripheral blood mononuclear cells (PBMCs) of patients with Graves' disease (GD). Thirty GD patients and 20 healthy controls were enrolled in this study. Global histone H3/H4 acetylation levels of PBMCs in all subjects were detected by enzyme-linked immunosorbent assay. mRNA levels of histone-related chromatin modifier genes were measured by real-time quantitative reverse transcription-polymerase chain reaction. Global histone H4 acetylation level in PBMCs of GD patients was significantly decreased compared with controls (p=0.005). The mRNA expression of histone deacetylases HDAC1 and HDAC2 were significantly increased in PBMCs of GD patients compared with controls (p=0.004 and 0.018; respectively). No significant difference was observed either in SIRT1 or in HATs mRNA including p300, CREBBP between GD patients and controls (p>0.05). Our findings firstly suggested that histone acetylation modifications are aberrant in PBMCs of GD patients, possibly due to the deregulation of epigenetic modifier genes.
Assuntos
Doença de Graves/genética , Doença de Graves/metabolismo , Histona Desacetilase 1/genética , Histona Desacetilase 2/genética , Histonas/sangue , Leucócitos Mononucleares/metabolismo , Acetilação , Adulto , Proteína de Ligação a CREB/sangue , Proteína de Ligação a CREB/genética , Epigênese Genética , Feminino , Regulação da Expressão Gênica , Doença de Graves/sangue , Histona Desacetilase 1/sangue , Histona Desacetilase 2/sangue , Humanos , Leucócitos Mononucleares/enzimologia , Masculino , Sirtuína 1/sangue , Sirtuína 1/genética , Fatores de Transcrição de p300-CBP/sangue , Fatores de Transcrição de p300-CBP/genéticaRESUMO
BACKGROUND: Several studies support a link between autoimmunity and interferon regulatory factor 5 (IRF5) gene polymorphisms. We have taken the opportunity to examine association of the autoimmune disease risk gene, the interferon regulatory factor 5 (IRF5) to survey its susceptibility to autoimmune thyroid disease. "A total of 667 patients with autoimmune thyroid diseases and 301 healthy controls were genotyped for rs10954213, rs2004640, rs3807306, rs752637 and rs7808907 of IRF5 gene polymorphisms". We further investigated the association between BANK1 gene and IRF5 gene in AITD patients. RESULTS: For IRF5 gene, both in allele and genotype frequencies from both GD and HT patients were not significantly different from those of controls. Association between rs7808907C allele and Graves' disease showed trend towards significance (P=0.067). Haplotype results in IRF5 represented in the same block, without significant association. No significant association was found between all IRF5 SNPs and ophthalmopathy in Graves' patients. Additive interaction analysis revealed no interactions between IRF5 and BANK1 gene in AITD patients. CONCLUSION: Our data fail to reveal IRF5 as a susceptibility gene to AITD and do not support additive effect of IRF5 to BANK1 gene.