Type 1 diabetes (T1D) is a common chronic disease of childhood associated with a significantly increased risk of micro- and macro-vascular complications, including neuropathy, nephropathy and cardiovascular diseases. The risk of development T1D comorbidities is associated with glycaemic control, a complex mechanism involving biological, physiological environmental factors. While more than 60 genetic variants were already associated with Glycated hemoglobin (HbA1c) in healthy subjects, very few genes have been identified in T1D individuals. Also, hyperglycaemia could be the cause of epigenetic changes at specific target genes, such as DNA methylation, histone modifications and microRNAs, correlated to accelerated development of diabetes-related complications. Most recently, increasing evidence also suggested that human microbiome may play a crucial role in the onset and progression of T1D and dysbiosis of the gut and oral microbiota was reported as a typical feature of hyperglycaemia. However, potential differences among poorly and good managed T1D subjects have not been still studied. Also, the exact mechanism by long-term hyperglycaemia's acts in T1D remains poorly understood. Therefore, this project will explore an emerging area of research by the study of possible genetic, epigenetic and environmental biomarkers among T1D subjects with different glycaemic control.
Study Type
OBSERVATIONAL
Enrollment
800
DNA genotyping, microbiome, DNA methylation and microRNAs analysis
Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"
Trieste, Italy
RECRUITINGIdentification of genes involved in T1D glycaemic control
DNA will be isolated from saliva by Genefix Saliva DNA/RNA collection kit (Isohelix, UK) and whole genome genotyping will be performed using Illumina chip arrays (CA, USA).
Time frame: Through study completion, an average of 18 months
Identification of DNA methylation patterns involved in T1D glycaemic control
Peripheral blood will be collected from each participant into EDTA-containing tubes and Genome-wide DNA methylation will be performed using the Illumina Infinium Human Methylation EPIC BeadChip array
Time frame: Through study completion, an average of 18 months
Identification of microRNAs involved in T1D glycaemic control
Peripheral blood will be collected from each participant into Ethylenediaminetetraacetic acid (EDTA)-containing tubes for microRNAs sequencing. Illumina TruSeq Small RNA Sample Preparation kit will be used for library preparation, and sequencing will be conducted by Illumina platform (CA, USA).
Time frame: Through study completion, an average of 18 months
Identification of oral microbiome characteristics associated to T1D glycaemic control
Bacterial DNA will be extracted from saliva and a 500 base pair region of the V1-V3 portion of the 16S ribosomal RNA gene as well as the 200 base pair region of the V3 portion will be amplified. The V3 amplicon will be used for template preparation and will be sequenced using the Ion PGM Hi-Q View sequencing kit (Life Technologies, New York, NY, USA) with the IonPGM™System technology
Time frame: Through study completion, an average of 18 months
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