DNA Methylation and Autoimmune Thyroid Diseases

NCT02491567 | Completed

• 1 other identifier: 62/17-2-2014
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hashimoto Thyroiditis; Graves Disease

Outcome Measures

Primary Outcomes (1)

• 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).

  1 month

Secondary Outcomes (33)

• Age

  1 day

• Age of disease onset

  1 day

• Sex

  1 day

• Body mass index

  1 day

• Pubertal stage

  1 day

Study Arms (3)

Hashimoto Thyroiditis (HT)

Children and adolescents with Hashimoto thyroiditis either hypothyroidic or euthyroidic.

Graves Disease (GD)

Children and adolescents with Graves Disease both those on remission and under antihyroid medication.

Controls (C)

Healthy individuals matched for gender and age without 1) any autoimmune disease 2) family history of autoimmune disease in the first degree relatives

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

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.

You may qualify if:

• For HT:
• A positive titers of antithyroid peroxidase (anti-TPO) or antithyroglobulin (anti-Tg) antibodies and at least one of:
• Abnormal thyroid function that requires substitution treatment with L-thyroxine (TSH \> 5 μIU/ml and decreased or normal levels of fT4 or fT3)
• Increased volume of thyroid gland (goiter)
• Morphological changes on ultrasound of the thyroid gland
• For GD:
• A positive titers of thyroid stimulating antibodies (anti-TSI) and
• Decreased TSH levels and increased levels of fT4 or fT3
• For Controls:
• Otherwise healthy children and adolescents, age- and gender-matched with patients
• Absence of previously known chronic disease of autoimmune aetiology or atopy (including those with a history of chronic treatment with antihistamines, anti-inflammatory, corticosteroids or anti-epileptic drugs)
• Absence of a family history of autoimmune disease in first-degree relatives

You may not qualify if:

• Not Caucasian origin or affinity among participants
• Age of diagnosis above 18 years
• Disease duration below 3 months

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead

Study Sites (1)

Unit of Pediatric Endocrinology, Diabetes and Metabolism-4th Department of Pediatrics, Medical School of Aristotle University of Thessaloniki

Thessaloniki, 56403, Greece

Location

Related Publications (13)

• Akirav EM, Lebastchi J, Galvan EM, Henegariu O, Akirav M, Ablamunits V, Lizardi PM, Herold KC. Detection of beta cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci U S A. 2011 Nov 22;108(47):19018-23. doi: 10.1073/pnas.1111008108. Epub 2011 Nov 9.

  PMID: 22074781 BACKGROUND

• Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, Julier C, Morahan G, Nerup J, Nierras C, Plagnol V, Pociot F, Schuilenburg H, Smyth DJ, Stevens H, Todd JA, Walker NM, Rich SS; Type 1 Diabetes Genetics Consortium. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet. 2009 Jun;41(6):703-7. doi: 10.1038/ng.381. Epub 2009 May 10.

  PMID: 19430480 BACKGROUND

• Cooper JD, Simmonds MJ, Walker NM, Burren O, Brand OJ, Guo H, Wallace C, Stevens H, Coleman G; Wellcome Trust Case Control Consortium; Franklyn JA, Todd JA, Gough SC. Seven newly identified loci for autoimmune thyroid disease. Hum Mol Genet. 2012 Dec 1;21(23):5202-8. doi: 10.1093/hmg/dds357. Epub 2012 Aug 24.

  PMID: 22922229 BACKGROUND

• Dang MN, Buzzetti R, Pozzilli P. Epigenetics in autoimmune diseases with focus on type 1 diabetes. Diabetes Metab Res Rev. 2013 Jan;29(1):8-18. doi: 10.1002/dmrr.2375.

  PMID: 23180441 BACKGROUND

• Davies TF, Latif R, Yin X. New genetic insights from autoimmune thyroid disease. J Thyroid Res. 2012;2012:623852. doi: 10.1155/2012/623852. Epub 2012 Feb 28.

  PMID: 22530160 BACKGROUND

• Fradin D, Le Fur S, Mille C, Naoui N, Groves C, Zelenika D, McCarthy MI, Lathrop M, Bougneres P. Association of the CpG methylation pattern of the proximal insulin gene promoter with type 1 diabetes. PLoS One. 2012;7(5):e36278. doi: 10.1371/journal.pone.0036278. Epub 2012 May 2.

  PMID: 22567146 BACKGROUND

• Huber A, Menconi F, Corathers S, Jacobson EM, Tomer Y. Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms. Endocr Rev. 2008 Oct;29(6):697-725. doi: 10.1210/er.2008-0015. Epub 2008 Sep 5.

  PMID: 18776148 BACKGROUND

• Lu Q. The critical importance of epigenetics in autoimmunity. J Autoimmun. 2013 Mar;41:1-5. doi: 10.1016/j.jaut.2013.01.010. Epub 2013 Feb 1.

  PMID: 23375849 BACKGROUND

• MacFarlane AJ, Strom A, Scott FW. Epigenetics: deciphering how environmental factors may modify autoimmune type 1 diabetes. Mamm Genome. 2009 Sep-Oct;20(9-10):624-32. doi: 10.1007/s00335-009-9213-6. Epub 2009 Aug 22.

  PMID: 19697079 BACKGROUND

• Quintero-Ronderos P, Montoya-Ortiz G. Epigenetics and autoimmune diseases. Autoimmune Dis. 2012;2012:593720. doi: 10.1155/2012/593720. Epub 2012 Mar 22.

  PMID: 22536485 BACKGROUND

• Rakyan VK, Beyan H, Down TA, Hawa MI, Maslau S, Aden D, Daunay A, Busato F, Mein CA, Manfras B, Dias KR, Bell CG, Tost J, Boehm BO, Beck S, Leslie RD. Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. PLoS Genet. 2011 Sep;7(9):e1002300. doi: 10.1371/journal.pgen.1002300. Epub 2011 Sep 29.

  PMID: 21980303 BACKGROUND

• Weetman AP. Determinants of autoimmune thyroid disease. Nat Immunol. 2001 Sep;2(9):769-70. doi: 10.1038/ni0901-769. No abstract available.

  PMID: 11526381 BACKGROUND

• Yin X, Latif R, Tomer Y, Davies TF. Thyroid epigenetics: X chromosome inactivation in patients with autoimmune thyroid disease. Ann N Y Acad Sci. 2007 Sep;1110:193-200. doi: 10.1196/annals.1423.021.

  PMID: 17911434 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be collected and centrifuged and then leukocytes will be separated. DNA will then be isolated from peripheral leukocytes using the QIAamp DNA Blood Mini Kit.

MeSH Terms

Conditions

Hashimoto Disease; Graves Disease

Condition Hierarchy (Ancestors)

Thyroiditis, Autoimmune; Thyroiditis; Thyroid Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Hyperthyroidism

Study Officials

• Assimina Galli-Tsinopoulou, Professor

  Medical School, Aristotle University of Thessaloniki

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR

Study Record Dates

• First Submitted: December 23, 2014
• First Posted: July 8, 2015
• Study Start: September 1, 2014
• Primary Completion: September 1, 2016
• Study Completion: April 1, 2018
• Last Updated: September 26, 2019

Record last verified: 2019-09

Locations

GR (1)