An observational study in Hashimoto Thyroiditis and Graves Disease, sponsored by Aristotle University Of Thessaloniki. Completed at 1 site in Greece. Open to participants aged 4 Years to 18 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-09-26.
Sponsored by Aristotle University Of Thessaloniki · Observational
Hashimoto Thyroiditis (HT) and Graves Disease (GD) are known to be caused by abnormal immune response against self cells and tissues. Epigenetics is a novel field of biology studying the mechanisms by which the environment interacts with the genotype to produce a variety of phenotypes through modifications to chromatin that do not directly alter the DNA sequence. A very limited number of epigenetic studies have been published in patients with HT and GD so far. Therefore, the purpose of this study is to analyze DNA methylation status in White Blood Cells (WBCs) within the promoter regions of genomic sites that have been previously identified as susceptibility loci or sites for autoimmune thyroid disease, such as the CD40L, FOXP3, CTLA4, PTPN22, IL2RA, FCRL3 and HLADRB1 genes.
Hashimoto Thyroiditis (HT) and Graves Disease (GD) are known to be caused by abnormal immune response against self cells and tissues. HT involves a cell-mediated autoimmune destruction of the thyroid leading to hypothyroidism. GD is caused by a process in which immune cells make stimulating antibodies against the thyroid stimulating hormone (TSH) receptor on the thyroid gland, thus leading to hyperthyroidism. Although there is substantial evidence that genetic factors increase the risk for developing autoimmune diseases, monozygotic twins still remain discordant for disease (disease concordance is never 100%), thus suggesting a role for environmental factors and epigenetics.
Epigenetics is a novel field of biology studying the mechanisms by which the environment interacts with the genotype to produce a variety of phenotypes through modifications to chromatin that do not directly alter the DNA sequence. These modifications have been associated with altered gene expression and silencing of repetitive elements and can be inherited mitotically. Epigenetic mechanisms include DNA methylation, histone modifications, or miRNA post-transcriptional regulation. DNA methylation involves the covalent addition of a methyl group to the carbon-5 position in the CpG dinucleotide from the methyl donor S-adenosylmethionine and is mediated by a group of enzymes called DNA methyltransferases (DNMTs). CpG dinucleotides are typically grouped together in regions known as CGIs (islands). CGIs can be found in the promoter regions of genes, and CpG methylation of these gene promoters is associated with transcriptional silencing. In contrast, hypermethylated genes have been found to be transcriptionally active.
A very limited number of epigenetic studies have been published in patients with HT and GD so far. Therefore, the purpose of this study is to analyze DNA methylation status in White Blood Cells (WBCs) within the promoter regions of genomic sites that have been previously identified as susceptibility loci or sites for autoimmune thyroid disease, such as the CD40L, FOXP3, CTLA4, PTPN22, IL2RA, FCRL3 and HLADRB1 genes.
Initially, recruitment of patients and controls as well as blood sample collection will be done. A complete physical examination will also be performed in all participants included in the study, and a detailed personal, family, gestational and perinatal history will be obtained as well before inclusion. Blood samples by all participants will be collected and centrifuged and then White Blood Cells (WBCs), plasma and serum will be separated and stored in a deep freezer.
Laboratory analyses will follow. DNA will be isolated from peripheral leukocytes using the QIAamp DNA Blood Mini Kit, according to the manufacturer's instructions. It will then be treated with sodium bisulfite using the Zymo EZ DNA Methylation-Gold Kit, again according to the manufacturer's protocol. Therefore, unmethylated cytosines will be converted into uracyls, whereas methylated cytosines will remain unchanged. Quantification of the methylation status of DNA at the gene promoter regions under study will be made, using specific primers that detect modified DNA, by real-time PCR and analysis of the melting curves of the selected fragments of DNA. Amplicons will also be analyzed by electrophoresis and visualized by ultraviolet trans-illumination.
An electronic Data Base will be constructed and Statistical Analysis will follow. Results and Conclusions will be published in peer-review journals and presented in International Meetings.
53 studies on the registry are indexed under Hashimoto Disease; 13 are open to participants now.
This study's enrollment of 110 is close to the median of 112 across 22 observational studies indexed under Hashimoto Disease.
Browse Hashimoto Disease studies →Aristotle University Of Thessaloniki is the lead sponsor of 282 studies on the registry; 55 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Children and adolescents of Greek origin, aged 4-18 years old with a diagnosis of Hashimoto Thyroiditis and Graves Disease as well as healthy controls.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For HT:
A positive titers of antithyroid peroxidase (anti-TPO) or antithyroglobulin (anti-Tg) antibodies and at least one of:
For GD:
For Controls:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Children and adolescents with Hashimoto thyroiditis either hypothyroidic or euthyroidic.
Children and adolescents with Graves Disease both those on remission and under antihyroid medication.
Healthy individuals matched for gender and age without 1) any autoimmune disease 2) family history of autoimmune disease in the first degree relatives
DNA methylation status of CpGs within gene promoters
Percentage of DNA methylation of CpGs within the CD40L, FOXP3, CTLA4, PTPN22, IL2RA, FCRL3 and HLADRB1 promoter genes in White Blood Cells (WBCs).
Time frame: 1 month
Age
Age of each participant
Time frame: 1 day
Age of disease onset
Age of disease diagnosis
Time frame: 1 day
Sex
Male or female
Time frame: 1 day
Body mass index
Weight in kg / height in m \* height in m
Time frame: 1 day
Pubertal stage
Prepubertal or pubertal stage
Time frame: 1 day
Antibodies titre
Titre of antiTPO, antiTg, anti-TSI antibodies in blood
Time frame: 1 day
Thyroid volume
Volume of the thyroid gland in total (both lobes)
Time frame: 1 day
Treatment dose
Dose of Levothyroxine/thiamazole per kg of body weight /per day (if applicable)
Time frame: 1 day
B12
Levels of B12 in blood
Time frame: 1 day
Folic acid
Levels of folic acid in blood
Time frame: 1 day
IgA, IgG, IgM, IgE immunoglobulins
Levels of IgA, IgG, IgM, IgE immunoglobulins in blood
Time frame: 1 day
History of infections
Number of previous febrile viral /bacterial infections per year
Time frame: 1 day
History of medications
Number of previous medications per year
Time frame: 1 day
Other autoimmune diseases
Diagnosis of co-existing autoimmune disease (except autoimmune thyroid disease)
Time frame: 1 day
Family history of autoimmune thyroid (or other) disease
Family history of autoimmune thyroid (or other) disease or not
Time frame: 1 day
Parental educational level
Elementary school, high school or university graduate
Time frame: 1 day
Type of Residence
Urban or rural residence
Time frame: 1 day
Parental smoking
Total number of cigarettes per day during their child's life separately for each parent (if applicable)
Time frame: 1 day
Previous births
Number of previous births
Time frame: 1 day
Month of birth
Month of birth (from January to December)
Time frame: 1 day
Delivery type
Cesarean section or vaginal delivery
Time frame: 1 day
Birth weight
Birth weight
Time frame: 1 day
Gestation duration
Duration of pregnancy
Time frame: 1 day
Medications during pregnancy
Number of medications of any type received during pregnancy (if applicable)
Time frame: 1 day
Maternal smoking during pregnancy
Total number of cigarettes per day during pregnancy (if applicable)
Time frame: 1 day
Maternal alcohol consumption during pregnancy
Total number of glasses of alcohol consumption per day during pregnancy (if applicable)
Time frame: 1 day
Pre-eclampsia (during pregnancy)
Diagnosis of pre-eclampsia (during pregnancy) or not
Time frame: 1 day
Gestational diabetes (during pregnancy)
Diagnosis of gestational diabetes (during pregnancy) or not
Time frame: 1 day
Vaginal bleeding (during pregnancy)
Presence of vaginal bleeding (during pregnancy) or not
Time frame: 1 day
Maternal febrile infection (during pregnancy)
Diagnosis of maternal febrile infection (during pregnancy) or not
Time frame: 1 day
Duration of breastfeeding
Duration of breastfeeding until discontinuance
Time frame: 1 day
History of phototherapy
History of phototherapy during neonatal period (or not)
Time frame: 1 day
APGAR score
APGAR score at 1st and 5th min of life
Time frame: 1 day
Ran from Sep 2014 to primary completion in Sep 2016, 24 months.
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This study is completed, as verified in Sep 2019. You cannot join it, but the record below documents what was studied.
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