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Evaluation and epigenetic impact of B12, vitamin D, folic acid and anemia in Hashimoto's thyroiditis: a clinical and molecular docking study

Year 2023, Volume: 6 Issue: 4, 705 - 712, 30.07.2023
https://doi.org/10.32322/jhsm.1243597

Abstract

Aims: Our approach in this study is to investigate the collective effect of various parameters, including vitamin B12 (B12), vitamin D (Vit-D), folic acid, and iron deficiency, on Hashimoto's thyroiditis (HT) disease. This differs from existing literature that has examined these parameters individually.
Methods: The study evaluated age, gender, thyroid stimulating hormone (TSH), free-T4 (FT4), free-T3 (FT3), Vit-D levels, as well as autoantibodies against thyroid peroxidase (anti-TPO) and anti-tyroglobulin iron (anti-TG) levels, ferritin, B12, and folic acid parameters in a total of 30 HT patients and 37 non-HT patients. These parameters were assessed by analyzing the patients' routine blood test results using automated analysis methods.
Results: A negative correlation was found between the blood, Vit-D level and anti-TG (as the vit-D value increases, the anti-TG decreases) (r=-0.417; p=0.001; p<0.01). There was a statistically significant and weak correlation between blood Vit-D measurements and anti-TPO measurements (r=-0.341; p=0.005; p<0.01).
Conclusion: The study findings demonstrated that there was no statistically significant difference in the measurements and correlation between hemoglobin, FT3, FT4, TSH, ferritin, vitamin B12, and folic acid levels in patients with and without a diagnosis of HT (p>0.05). However, the study emphasized the critical role of vitamin D in the pathophysiology and treatment of HT. Furthermore, molecular docking simulations indicated that folic acid could potentially act as a potent inhibitor of human extracellular signal-regulated kinase (ERK2), which has been reported to play a key role in HT.

Thanks

I can acknowledge the all authors. The support of Dr. Abdulilah Ece is gratefully acknowledged in computational part.

References

  • Ragusa F, Fallahi P, Elia G, et al. Hashimotos’ thyroiditis: epidemiology, pathogenesis, clinic and therapy. Best Practice Res Clin Endocrinol Metab. 2019;33(6):101367.
  • McLeod DS, Caturegli P, Cooper DS, et al. Variation in rates of autoim- mune thyroid disease by race/ethnicity in US military personnel. JAMA. 2014;311(15):1563–1565.
  • Rayman MP. Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease. Proc Nutr Soc. 2019;78(1):34-44.
  • Kawicka A, Regulska-Ilow B. Metabolic disorders and nutritional status in autoimmune thyroid diseases. Advances in Hygiene & Experimental Medicine/Postepy Higieny i Medycyny Doswiadczalnej. 2015;69:80-90.
  • Öztekin, Y, Ayaz A. Otoimmün tiroid hastalıklarında D vitamininin Rolü. İzmir Katip Çelebi Üniversitesi Sağlık Bilimleri Fakültesi Derg. 2015;7(1):179-184.
  • Wiersinga WM. Clinical relevance of envi- ronmental factors in the pathogenesis of au- toimmune thyroid disease. Endocrinol Metab. 2016;31(2):213-222.
  • Zaletel K, Gaberscek S. Hashimoto's thyroiditis:from genes to the disease. Curr Genomics. 2011;12(8):576-588.
  • Aktaş HŞ. Vitamin B12 and Vitamin D levels in patients with autoimmune hypothyroidism and their correlation with anti-thyroid peroxidase antibodies. Med Princ Pract. 2020;29(4);364-370.
  • Elvira D. The Role of T-Regulatory Expression in Autoimmune Thyroid Disease and its association with Thyroid antibody. J Autoim Disor. 2016;2;2:19.
  • Krysia R, Szkróbka W, Okopień B. The effect of vitamin D on thyroid autoimmunity in levothyroxine-treated women with Hashimoto’s thyroiditis and normal vitamin D status. Exp Clin Endocrinol Diabetes. 2017;125(4):229-233.
  • Hu S, Rayman MP. Multiple nutritional factors and the risk of Hashimoto's thyroiditis. Thyroid. 2017;27(5):597-610.
  • Ashraf TS, De Sanctis V, Yassin M, Wagdy M, & Soliman N. Chronic anemia and thyroid function. Acta Bio Medica: Atenei Parmensis. 2017;88(1):119.
  • Koç Ş, Güngör K, Güngör ND, Uzunlulu M. Iron deficiency in women with thyroid-specific autoantibodies:a case control study. J Exp Clin Med. 2022;39(1):194-198.
  • Das P, Dasnayak G, Senapati U. Cytomorphological spectrum of Hashimoto's thyroiditis and its correlatıon with clinical presentation, thyroid function test and antibody level. Int J Sci Res. 2018;7:2277-2282.
  • Rosen Y, Daich J, Soliman I, Brathwaite E, Shoenfeld Y. Vitamin D and autoimmunity. Scand J Rheumatol. 2016;45(6):439–447.
  • Kivity S, Agmon-Levin N, Zisappl M, et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. 2011;8(3):243–247.
  • Unal AD, Tarcin O, Parildar H, et al. Vitamin D deficiency is related to thyroid antibodies in autoimmune thyroiditis. Cent Eur J Immunol. 2014;39(4):493–497.
  • Kim D. The role of vitamin D in thyroid diseases. Int J Mol Sci. 2017;18(9):1949.
  • Mele C, Caputo M, Bisceglia A, et al. Immunomodulatory effects of vitamin D in thyroid diseases. Nutrients. 2020;12(5):1444.
  • Rubens M, Ramamoorthy V, Saxena P, et al. Association between vitamin D deficiency and hypothyroidism:results from the National Health and Nutrition Examination Survey (NHANES). 2007–2012. BMC Endocr Disord. 2021;21(1):1-9.
  • Ece A, Sevin F. Exploring QSAR on 4-cyclohexylmethoxypyrimidines as antitumor agents for their inhibitory activity of cdk2. Letters in Drug Design & Discovery. 2010;7:625-631.
  • Chan K, Frankish N, Zhang T, et al. Bioactive indanes:insight into the bioactivity of indane dimers related to the lead anti-inflammatory molecule PH46A. J Pharm Pharmacol. 2020;72(7):927-937.
  • Yamali C, Gul HI, Sakarya M.T, et al. Quinazolinone-based benzenesulfonamides with low toxicity and high affinity as monoamine oxidase-A inhibitors:synthesis, biological evaluation and induced-fit docking studies. Bioor Chem. 2022;124:105822.
  • Luo X, Zheng T, Mao C, et al. Aberrant MRP14 expression in thyroid follicular cells mediates chemokine secretion through the IL-1β/MAPK pathway in Hashimoto’s thyroiditis. Endocr Connect. 2018;7(6):850-858.
  • Gan XX, Zhong LK, Shen F, et al. Network pharmacology to explore the molecular mechanisms of prunella vulgaris for treating Hashimoto’s thyroiditis. Front Pharmacol. 2021:12.
  • Beyazit Y, Kocak E, Tanoglu A, Kekilli M. Oxidative stress might play a role in low serum vitamin D associated liver fibrosis among patients with autoimmune hepatitis. Dig Dis Sci. 2015;60(4):1106-1108.

Evaluation and epigenetic impact of B12, vitamin D, folic acid and anemia in Hashimato's thyroiditis

Year 2023, Volume: 6 Issue: 4, 705 - 712, 30.07.2023
https://doi.org/10.32322/jhsm.1243597

Abstract

Aim:This study aimed to evaluate the frequency of B12, vitamin D, folic acid and iron deficiency, which play a role in the pathogenesis and epigenetic effect on HT, compared to individuals without thyroid disease. Materials and Methods:Age, gender, thyroid stimulating hormone (TSH), free-T4 (FT4), free-T3 (FT3), vit-D among 30 HT patients and 37 non-HT patients admitted to the outpatient clinic between January and December 2021, anti-TPO and Anti-Tyroglobulin iron, vit-D, ferritin, B12, folic acid parameters were evaluated by checking the patients routine blood test results taken by autoanalysis between groups. Results:When the vit-D levels of 30 patients with HT and 37 patients without a diagnosis of HT were compared, a difference was found between vit-D levels. A negative correlation was found between the blood, vit-D level and Anti-TG (as the vit-D value increases, the Anti-Tyroglobulin value decreases) (r=-0.417; p=0.001; p<0.01). There was a statistically significant and weak correlation between blood vit-D measurements and Anti-TPO measurements (r=-0.341; p=0.005; p<0.01). Conclusion:When evaluated in terms of Hemoglobin, FT3, FT4, TSH, Ferritin, Vitamin B12, and Folic acid between patients with and without a diagnosis of HT, their measurements did not show a statistically significant difference (p>0.05). Once again, the importance of vit-D deficiency in the physiopathology and treatment of HT, the elimination of vit-D deficiency have actually been shown how important in the treatment process of HT. On the other hand, molecular docking simulations revealed that folic acid might be a strong inhibitor of human extracellular signal-regulated kinase (ERK2) which was reported to have a key role in HT.

References

  • Ragusa F, Fallahi P, Elia G, et al. Hashimotos’ thyroiditis: epidemiology, pathogenesis, clinic and therapy. Best Practice Res Clin Endocrinol Metab. 2019;33(6):101367.
  • McLeod DS, Caturegli P, Cooper DS, et al. Variation in rates of autoim- mune thyroid disease by race/ethnicity in US military personnel. JAMA. 2014;311(15):1563–1565.
  • Rayman MP. Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease. Proc Nutr Soc. 2019;78(1):34-44.
  • Kawicka A, Regulska-Ilow B. Metabolic disorders and nutritional status in autoimmune thyroid diseases. Advances in Hygiene & Experimental Medicine/Postepy Higieny i Medycyny Doswiadczalnej. 2015;69:80-90.
  • Öztekin, Y, Ayaz A. Otoimmün tiroid hastalıklarında D vitamininin Rolü. İzmir Katip Çelebi Üniversitesi Sağlık Bilimleri Fakültesi Derg. 2015;7(1):179-184.
  • Wiersinga WM. Clinical relevance of envi- ronmental factors in the pathogenesis of au- toimmune thyroid disease. Endocrinol Metab. 2016;31(2):213-222.
  • Zaletel K, Gaberscek S. Hashimoto's thyroiditis:from genes to the disease. Curr Genomics. 2011;12(8):576-588.
  • Aktaş HŞ. Vitamin B12 and Vitamin D levels in patients with autoimmune hypothyroidism and their correlation with anti-thyroid peroxidase antibodies. Med Princ Pract. 2020;29(4);364-370.
  • Elvira D. The Role of T-Regulatory Expression in Autoimmune Thyroid Disease and its association with Thyroid antibody. J Autoim Disor. 2016;2;2:19.
  • Krysia R, Szkróbka W, Okopień B. The effect of vitamin D on thyroid autoimmunity in levothyroxine-treated women with Hashimoto’s thyroiditis and normal vitamin D status. Exp Clin Endocrinol Diabetes. 2017;125(4):229-233.
  • Hu S, Rayman MP. Multiple nutritional factors and the risk of Hashimoto's thyroiditis. Thyroid. 2017;27(5):597-610.
  • Ashraf TS, De Sanctis V, Yassin M, Wagdy M, & Soliman N. Chronic anemia and thyroid function. Acta Bio Medica: Atenei Parmensis. 2017;88(1):119.
  • Koç Ş, Güngör K, Güngör ND, Uzunlulu M. Iron deficiency in women with thyroid-specific autoantibodies:a case control study. J Exp Clin Med. 2022;39(1):194-198.
  • Das P, Dasnayak G, Senapati U. Cytomorphological spectrum of Hashimoto's thyroiditis and its correlatıon with clinical presentation, thyroid function test and antibody level. Int J Sci Res. 2018;7:2277-2282.
  • Rosen Y, Daich J, Soliman I, Brathwaite E, Shoenfeld Y. Vitamin D and autoimmunity. Scand J Rheumatol. 2016;45(6):439–447.
  • Kivity S, Agmon-Levin N, Zisappl M, et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. 2011;8(3):243–247.
  • Unal AD, Tarcin O, Parildar H, et al. Vitamin D deficiency is related to thyroid antibodies in autoimmune thyroiditis. Cent Eur J Immunol. 2014;39(4):493–497.
  • Kim D. The role of vitamin D in thyroid diseases. Int J Mol Sci. 2017;18(9):1949.
  • Mele C, Caputo M, Bisceglia A, et al. Immunomodulatory effects of vitamin D in thyroid diseases. Nutrients. 2020;12(5):1444.
  • Rubens M, Ramamoorthy V, Saxena P, et al. Association between vitamin D deficiency and hypothyroidism:results from the National Health and Nutrition Examination Survey (NHANES). 2007–2012. BMC Endocr Disord. 2021;21(1):1-9.
  • Ece A, Sevin F. Exploring QSAR on 4-cyclohexylmethoxypyrimidines as antitumor agents for their inhibitory activity of cdk2. Letters in Drug Design & Discovery. 2010;7:625-631.
  • Chan K, Frankish N, Zhang T, et al. Bioactive indanes:insight into the bioactivity of indane dimers related to the lead anti-inflammatory molecule PH46A. J Pharm Pharmacol. 2020;72(7):927-937.
  • Yamali C, Gul HI, Sakarya M.T, et al. Quinazolinone-based benzenesulfonamides with low toxicity and high affinity as monoamine oxidase-A inhibitors:synthesis, biological evaluation and induced-fit docking studies. Bioor Chem. 2022;124:105822.
  • Luo X, Zheng T, Mao C, et al. Aberrant MRP14 expression in thyroid follicular cells mediates chemokine secretion through the IL-1β/MAPK pathway in Hashimoto’s thyroiditis. Endocr Connect. 2018;7(6):850-858.
  • Gan XX, Zhong LK, Shen F, et al. Network pharmacology to explore the molecular mechanisms of prunella vulgaris for treating Hashimoto’s thyroiditis. Front Pharmacol. 2021:12.
  • Beyazit Y, Kocak E, Tanoglu A, Kekilli M. Oxidative stress might play a role in low serum vitamin D associated liver fibrosis among patients with autoimmune hepatitis. Dig Dis Sci. 2015;60(4):1106-1108.
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Details

Primary Language English
Subjects Endocrinology, Health Care Administration
Journal Section Original Article
Authors

Elif Sibel Aslan 0000-0002-3081-9004

Savaş Gür 0000-0003-1818-4795

Early Pub Date July 28, 2023
Publication Date July 30, 2023
Published in Issue Year 2023 Volume: 6 Issue: 4

Cite

AMA Aslan ES, Gür S. Evaluation and epigenetic impact of B12, vitamin D, folic acid and anemia in Hashimoto’s thyroiditis: a clinical and molecular docking study. J Health Sci Med / JHSM. July 2023;6(4):705-712. doi:10.32322/jhsm.1243597

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