Original Article

Increased Mitochondrial DNA Copy Number and Oxidative Damage in Patients with Hashimoto’s Thyroiditis


Background: The purpose of present study was to investigate mitochondrial DNA copy number (mtDNAcn) and mtDNA damage in peripheral blood of patients with Hashimoto's thyroiditis (HT) and healthy controls (HC).

Methods: The relative mtDNAcn and oxidative DNA damage in this case-control study were measured in peripheral blood of 50 patients with Hashimoto’s thyroiditis and 50 healthy controls using quantitative real-time PCR. The study was conducted in Tehran University of Medical Sciences hospital, Tehran, Iran in 2018.

Results: HT patients had significantly higher mitochondrial DNA copy number and mitochondrial oxidative damage than the comparison group.

Conclusion: These data suggest the possible involvement of mitochondria and oxidative stress in the pathophysiology of HT.

1. Shukla SK, Singh G, Ahmad S et al (2018). Infections, genetic and environmental factors in pathogenesis of autoimmune thyroid diseases. Microb Pathog, 116:279-88.
2. Mseddi M, Ben Mansour R, Gargouri B et al (2017). Proteins oxidation and autoanti-bodies' reactivity againsthydrogen perox-ide and malondialdehyde -oxidized thy-roid antigens in patients' plasmas with Graves' disease and Hashimoto thyroidi-tis. Chem Biol Interact, 272:145-52.
3. Mseddi M, Ben Mansour R, Gouiia N et al (2017). A comparative study of nuclear 8-hydroxyguanosine expression in Auto-immune Thyroid Diseases and Papillary Thyroid Carcinoma and its relationship with p53, Bcl-2 and Ki-67 cancer related proteins. Adv Med Sci, 62 (1):45-51.
4. Ruggeri RM, Vicchio TM, Cristani M et al (2016). Oxidative stress and advanced glycation end products in Hashimoto's thyroiditis. Thyroid, 26:504-11.
5. Yehuda-Shnaidman E, Kalderon B, Bar-Tana J (2014). Thyroid hormone, thyro-mimetics, and metabolic efficiency. Endocr Rev, 35 (1):35-58.
6. Lanni A, Moreno M, Goglia F (2016). Mito-chondrial actions of thyroid hormone. Compr Physiol, 6 (4):1591-607.
7. Athéa Y, Garnier A, Fortin D et al (2007). Mitochondrial and energetic cardiac phe-notype in hypothyroid rat. Relevance to heart failure. Pflugers Arch, 455 (3):431-42.
8. Herbers E, Kekäläinen NJ, Hangas A et al (2019). Tissue specific differences in mi-tochondrial DNA maintenance and ex-pression. Mitochondrion, 44:85-92.
9. Vaseghi H, Houshmand M, Jadali Z (2017). Increased levels of mitochondrial DNA copy number in patients with vitiligo. Clin Exp Dermatol, 42 (7):749-54.
10. Kalsbeek AMF, Chan EKF, Grogan J et al (2018). Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer. Prostate, 78 (1):25-31.
11. Lee HC, Wei YH (2005). Mitochondrial bio-genesis and mitochondrial DNA mainte-nance of mammalian cells under oxida-tive stress. Int J Biochem Cell Biol, 37 (4): 822-34.
12. Bogenhagen DF (2012). Mitochondrial DNA nucleoid structure. Biochim Biophys Acta, 1819 (9-10):914-20.
13. Akhmedov AT, Marín-García J (2015). Mi-tochondrial DNA maintenance: an ap-praisal. Mol Cell Biochem, 409 (1-2):283-305.
14. Van Houten B , Santa-Gonzalez GA, Ca-margo M (2018). DNA repair after oxida-tive stress: current challenges. Curr Opin Toxicol, 7:9-16.
15. Yang X, Wang XB, Vorpagel ER et al (2004). Direct experimental observation of the low ionization potentials of gua-nine in free oligonucleotides by using photoelectron spectroscopy. Proc Natl Acad Sci U S A, 101 (51):17588-92.
16. Smith CC, O'Donovan MR, Martin EA (2006). hOGG1 recognizes oxidative damage using the comet assay with great-er specificity than FPG or ENDOIII. Mu-tagenesis, 21 (3):185-90.
17. Karakaya A, Jaruga P, Bohr VA et al (1997). Kinetics of excision of purine lesions from DNA by Escherichia coli Fpg pro-tein. Nucleic Acids Res, 25 (3):474-9.
18. VO'Connor TR, Laval J (1989). Physical as-sociation of the 2, 6-diamino-4-hydroxy-5N-formamidopyrimidine-DNA glyco-sylase of Escherichia coli and an activity nicking DNA at apurinic/apyrimidinic sites. Proc Natl Acad Sci U S A, 86(14):5222-6.
19. Wallace SS (2002). Biological consequences of free radical-damaged DNA bases. Free Radic Biol Med, 33 (1):1-14.
20. Liguori I, Russo G, Curcio F et al (2018). Oxidative stress, aging, and diseases. Clin Interv Aging, 13:757-772.
21. Dalle-Donne I, Rossi R, Colombo R et al (2006). Biomarkers of oxidative damage in human disease. Clin Chem, 52 (4):601-23.
22. Garcia I, Jones E, Ramos M et al (2017). The little big genome: the organization of mitochondrial DNA. Front Biosci (Land-mark Ed), 22:710-721.
23. Kuznetsova T, Knez J (2017). Peripheral blood Mitochondrial DNA and myocar-dial function. Adv Exp Med Biol, 982:347-58.
24. Valavanidis A, Vlachogianni T, Fiotakis C (2009). 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 27 (2):120-39.
25. Varma VA, Cerjan CM, Abbott KL et al (1994). Non-isotopic in situ hybridization method for mitochondria in oncocytes. J Histochem Cytochem, 42 (2):273-6.
26. Zimmermann FA, Neureiter D, Feichtinger RG et al (2016). Deficiency of respiratory chain complex I in Hashimoto thyroiditis. Mitochondrion, 26:1-6.
27. Wiesner RJ, Kurowski TT, Zak R (1992). Regulation by thyroid hormone of nucle-ar and mitochondrial genes encoding subunits of cytochrome-c oxidase in rat liver and skeletal muscle. Mol Endocrinol, 6 (9):1458-67.
28. Siciliano G, Monzani F, Manca ML et al (2002). Human mitochondrial transcrip-tion factor A reduction and mitochondri-al dysfunction in Hashimoto's hypothy-roid myopathy. Mol Med, 8 (6):326-33.
29. Altan N, Sepici-Dinçel A, Sahin D et al (2010). Oxidative DNA damage: the thy-roid hormone-mediated effects of insulin on liver tissue. Endocrine, 38 (2):214-20.
30. Ece H, Mehmet E, Cigir BA et al (2013). Se-rum 8-OHdG and HIF-1α levels: do they affect the development of malignancy in patients with hypoactive thyroid nodules? Contemp Oncol (Pozn), 17 (1):51-7.
31. López-Torres M, Romero M, Barja G (2000). Effect of thyroid hormones on mitochondrial oxygen free radical pro-duction and DNA oxidative damage in the rat heart. Mol Cell Endocrinol, 168 (1-2):127-34.
32. Hara H, Sato R, Ban Y (2001). Production of 8-OHdG and cytochrome c by cultured human mononuclear cells in patients with autoimmune thyroid disease. Endocr J, 48 (6):671-5.
33. Qiu YL, Zhu H, Ma SG et al (2015). Evalua-tion of inflammatory and oxidative bi-omarkers in children with well-controlled congenital hypothyroidism. J Pediatr Endo-crinol Metab, 28 (7-8):761-5.
34. Fernández-Vizarra E, Enriquez JA, Pérez-Martos A et al (2008). Mitochondrial gene expression is regulated at multiple levels and differentially in the heart and liver by thyroid hormones. Curr Genet, 54:13-22.
35. Hoch FL (1968). Biochemistry of hyperthy-roidism and hypothyroidism. Postgrad Med J, 44 (511):347-62.
36. Vaitkus JA, Farrar JS, Celi FS (2015). Thy-roid hormone mediated modulation of energy expenditure. Int J Mol Sci, 16 (7):16158-75.
37. Mishra P, Samanta L (2012). Oxidative stress and heart failure in altered thyroid States. ScientificWorldJournal, 2012:741861.
38. Kvetny J, Wilms L, Pedersen PL et al (2010). Subclinical hypothyroidism affects mito-chondrial function. Horm Metab Res, 42 (5):324-7.
39. Venditti P, De Rosa R, Di Meo S (2003). Ef-fect of thyroid state on susceptibility to oxidants and swelling of mitochondria from rat tissues. Free Radic Biol Med, 35 (5):485-94.
40. Wachsmuth M, Hübner A, Li M et al (2016). Age-related and heteroplasmy-related var-iation in human mtDNA copy number. PLoS Genet, 12 (3):e1005939.
41. Knez J, Winckelmans E, Plusquin M et al (2016). Correlates of peripheral blood mi-tochondrial DNA content in a general population. Am J Epidemiol, 183 (2):138-46.
42. Armengol MP, Cardoso-Schmidt CB, Fer-nández M et al (2003). Chemokines de-termine local lymphoneogenesis and a reduction of circulating CXCR4+ T and CCR7 B and T lymphocytes in thyroid autoimmune diseases. J Immunol, 170 (12):6320-8.
IssueVol 50 No 8 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v50i8.6817
Mitochondrial DNA Hashimoto's thyroiditis Oxidative stress Autoimmunity

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How to Cite
Esfahanian F, Mirabdolhagh Hazaveh M, Hooshmand Garehbagh L, Falahati K, Ataei M, Sanati MH, Jadali Z. Increased Mitochondrial DNA Copy Number and Oxidative Damage in Patients with Hashimoto’s Thyroiditis. Iran J Public Health. 2021;50(8):1697-1704.