RESUMO
In the light of growing global epidemic of type 2 diabetes mellitus (T2DM), significant efforts are made to discover next-generation biomarkers for early detection of the disease. Multiple mechanisms including inflammatory response, abnormal insulin secretion and glucose metabolism contribute to the development of T2DM. Platelet activation, on the other hand, is known to be one of the underlying mechanisms of atherosclerosis, which is a common T2DM complication that frequently results in ischemic events at later stages of the disease. Available data suggest that platelets contain large amounts of microRNAs (miRNAs) that are found in circulating body fluids, including the blood. Since miRNAs have been illustrated to play an important role in metabolic homeostasis through regulation of multiple genes, they attracted substantial scientific interest as diagnostic and prognostic biomarkers in T2DM. Various miRNAs, as well as their target genes are implicated in the complex pathophysiology of T2DM. This article will first review the different miRNAs studied in the context of T2DM and platelet reactivity, and subsequently present original results from bioinformatic analyses of published reports, identifying a common gene (PRKAR1A) linked to glucose metabolism, blood coagulation and insulin signalling and targeted by miRNAs in T2DM. Moreover, miRNA-target gene interaction networks built upon Gene Ontology information from electronic databases were developed. According to our results, miR-30a-5p, miR-30d-5p and miR-30c-5p are the most widely regulated miRNAs across all specified ontologies, hence they are the most promising biomarkers of T2DM to be investigated in future clinical studies.
Assuntos
Glicemia/genética , Plaquetas/metabolismo , MicroRNA Circulante/sangue , Biologia Computacional , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/sangue , Diabetes Mellitus Tipo 2/sangue , Ativação Plaquetária/genética , Glicemia/metabolismo , MicroRNA Circulante/genética , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Bases de Dados Genéticas , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Marcadores Genéticos , Humanos , Mapas de Interação de ProteínasRESUMO
BACKGROUND: Expression quantitative trait loci (eQTL) play an important role in the regulation of gene expression. Gene expression levels and eQTLs are expected to vary from tissue to tissue, and therefore multi-tissue analyses are necessary to fully understand complex genetic conditions in humans. Dura mater tissue likely interacts with cranial bone growth and thus may play a role in the etiology of Chiari Type I Malformation (CMI) and related conditions, but it is often inaccessible and its gene expression has not been well studied. A genetic basis to CMI has been established; however, the specific genetic risk factors are not well characterized. RESULTS: We present an assessment of eQTLs for whole blood and dura mater tissue from individuals with CMI. A joint-tissue analysis identified 239 eQTLs in either dura or blood, with 79% of these eQTLs shared by both tissues. Several identified eQTLs were novel and these implicate genes involved in bone development (IPO8, XYLT1, and PRKAR1A), and ribosomal pathways related to marrow and bone dysfunction, as potential candidates in the development of CMI. CONCLUSIONS: Despite strong overall heterogeneity in expression levels between blood and dura, the majority of cis-eQTLs are shared by both tissues. The power to detect shared eQTLs was improved by using an integrative statistical approach. The identified tissue-specific and shared eQTLs provide new insight into the genetic basis for CMI and related conditions.
Assuntos
Malformação de Arnold-Chiari/genética , Locos de Características Quantitativas , Adolescente , Malformação de Arnold-Chiari/patologia , Desenvolvimento Ósseo/genética , Criança , Pré-Escolar , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/sangue , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Dura-Máter/metabolismo , Feminino , Redes Reguladoras de Genes , Genótipo , Humanos , Masculino , Pentosiltransferases/sangue , Pentosiltransferases/genética , Pentosiltransferases/metabolismo , Polimorfismo de Nucleotídeo Único , beta Carioferinas/sangue , beta Carioferinas/genética , beta Carioferinas/metabolismo , UDP Xilose-Proteína XilosiltransferaseRESUMO
RATIONALE: Cardiac myxoma is the most common cardiac neoplasm. Currently, there are not many reports on familial cardiac myxoma. Herein, we reported 2 first-degree relatives with left atrial myxoma. PATIENT CONCERNS: A 20-year-old female was admitted in our hospital for lapsing into a coma for 24âhours, and was diagnosed with recurrent left atrial cardiac myxoma. The patient's father also had a history of cardiac myxoma. DIAGNOSIS: The patient was diagnosed with left atrial myxoma using transthoracic echocardiography (TTE). Whole exome sequencing (WES) identified a p.Val164Aspfs (c.491-492delTG) mutation in the cAMP-dependent protein kinase A (PKA) regulatory (R) subunit 1 (PRKAR1A) gene for both the proband and her father, but not in her uncle and brother, who had not shown manifestation of cardiac myxoma by the time of this report. INTERVENTIONS: The myxoma resection was performed following the standard procedure of open chest surgery. OUTCOMES: The tumor was successfully removed along with the tuberculum. The patient recovered well and was discharged home. No recurrence occurred during 1-year follow-up. LESSONS: Our findings suggest that PRKAR1A mutation (c.491_492delTG) may be associated with cardiac myxoma, and genetic counseling and specific locus mutation tests may contribute to assessing the risk of cardiac myxoma.