VITAMIN D LEVELS AND VDR rs2228570 GENETIC VARIANT IN AUTOIMMUNE THYROIDITIS

Aleena Parveen Shaikh; Nameera Parveen Shaikh; Irina Nakashidze

doi:10.5937/sanamed0-46407

Aleena Parveen Shaikh Batumi Shota Rustaveli State University, Batumi, Georgia
Nameera Parveen Shaikh Batumi Shota Rustaveli State University, Batumi, Georgia
Irina Nakashidze Batumi Shota Rustaveli State University, Batumi, Georgia

DOI: https://doi.org/10.5937/sanamed0-46407

Keywords: VDR Gene, SNP, Vitamin D, Autoimmune Thyroiditis

Abstract

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disorder characterized by an immune response targeting the thyroid gland. Genetic factors play a significant role in AIT susceptibility, with immune-related genes, especially the vitamin D receptor (VDR) gene, potentially influencing AIT development. This comprehensive review delves into the intricate association between VDR gene polymorphisms, particularly rs2228570 (FokI), and AIT susceptibility, exploring various populations. Research has unveiled contrasting outcomes regarding the link between the VDR rs2228570 polymorphism and AIT risk across diverse ethnic groups. Certain populations have exhibited a noteworthy correlation, suggesting that population-specific genetic factors contribute to AIT risk. A recurring observation of vitamin D deficiency in AIT patients has correlated with elevated anti-thyroid antibodies, abnormal thyroid function, and thyroid volume. The results emphasize the possible role of vitamin D in the development of AIT, suggesting the importance of vitamin D supplementation to address deficiencies associated with AIT. In addition to VDR rs2228570, other genetic variants have also shown associations with AIT susceptibility, displaying varying results across different populations. Ethnicity emerges as a pivotal factor influencing these associations, underscoring the need to consider genetic variations in diverse populations. We emphasize the intricate interplay between VDR gene polymorphisms, vitamin D, and AIT susceptibility. Extensive research is essential to unveil the clinical significance of these genetic variations, offering prospects for enhanced diagnostic and therapeutic strategies for individuals with AIT.

Author Biographies

Aleena Parveen Shaikh , Batumi Shota Rustaveli State University, Batumi, Georgia

ORCID: 0000-0002-1473-4334

Nameera Parveen Shaikh , Batumi Shota Rustaveli State University, Batumi, Georgia

ORCID: 0000-0002-7393-0263

Irina Nakashidze, Batumi Shota Rustaveli State University, Batumi, Georgia

ORCID: 0000-0001-8934-6312

References

Santoro D, Vadalà C, Siligato R, Buemi M, Benvenga S. Autoimmune thyroiditis and glomerulopathies. Front Endocrinol. 2017;8:119. doi: 10.3389/fendo.2017.00119.

Fallahi P, Ferrari SM, Antonelli A. Autoimmune thyroiditis. In: Gu D, Dupre ME, editors. Encyclopedia of gerontology and population aging. Cham: Springer International Publishing; 2021. p. 563–72. Available from: https://doi.org/10.1007/978-3-030-22009-9_63.

Wang B, Shao X, Song R, Xu D, Zhang JA. The emerging role of epigenetics in autoimmune thyroid diseases. Front Immunol. 2017;8:396. doi: 10.3389/fimmu.2017.00396.

Zhang C, Qin L, Sun B, Wu Y, Zhong F, Wu L, et al. Transcriptome analysis of the effect of diosgenin on autoimmune thyroiditis in a rat model. Sci Rep. 2021;11(1):6401. doi:10.1038/s41598-021-85822-1.

Balázs C. Örökletes és környezeti tényezők szerepe autoimmun pajzsmirigybetegségekben [The role of hereditary and environmental factors in autoimmune thyroid diseases]. Orv Hetil. 2012;153(26):1013-22. Hungarian. doi: 10.1556/OH.2012.29370.

Ferrari SM, Fallahi P, Antonelli A, Benvenga S. Environmental issues in thyroid diseases. Front Endocrinol (Lausanne). 2017;8:50. doi: 10.3389/fendo.2017.00050.

Brent GA. Environmental exposures and autoimmune thyroid disease. Thyroid. 2010 ;20(7):755–61. doi: 10.1089/thy.2010.1636.

Weider T, Genoni A, Broccolo F, Paulsen TH, Dahl-Jørgensen K, Toniolo A, et al. High prevalence of common human viruses in thyroid tissue. Front Endocrinol. 2022;13:938633. doi:10.3389/fendo.2022.938633.

Kravchenko V, Zakharchenko T. Thyroid hormones and minerals in immunocorrection of disorders in autoimmune thyroid diseases. Front Endocrinol. 2023;14:1225494. doi: 10.3389/fendo.2023.1225494.

Maciejewski A, Kowalczyk MJ, Herman W, Czyżyk A, Kowalska M, Żaba R, et al. Vitamin D receptor gene polymorphisms and autoimmune thyroiditis: are they associated with disease occurrence and its features? Bio Med Res Int. 2019;2019:8197580. doi: 10.1155/2019/8197580.

Shaikh AP, Shaikh NP, Irina N. VDR Gene SNPs in Gastrointestinal Tumors. JSM Gastroenterol Hepatol.2022; 9(2): 1111.

Apaydın M, Beysel S, Eyerci N, Pinarli FA, Ulubay M, Kizilgul M, et al. The VDR gene FokI polymorphism is associated with gestational diabetes mellitus in Turkish women. BMC Med Genet. 2019;20(1):82. doi: 10.1186/s12881-019-0820-0.

Albi E, Borrelli A, Cataldi S, Ceccarini M, Nakashidze I, Codini M et al. Protective effect of rMnSOD in mice exposed to cosmonaut simulation radiation: involvement of vitamin D receptor. J Biotechnol. 2019;305:S64. doi: 10.1016/j.jbiotec.2019.05.226.

Zhang R, Naughton DP. Vitamin D in health and disease: current perspectives. Nutr J. 2010;9:1-3. doi: 10.1186/1475-2891-9-65.

Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab. 2009;94(1):26-34. doi:10.1210/jc.2008-1454.

Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25- dihydroxyvitamin D3 on human B cell differentiation. J Immunol. 2007;179(3):1634–47. doi:10.4049/jimmunol.179.3.1634.

Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dankó K, et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. 2011;8(3):243–7. doi:10.1038/cmi.2010.73.

Bozkurt NC, Karbek B, Ucan B, Sahin M, Cakal E, Ozbek M, et al. The association between severity of vitamin D deficiency and Hashimoto’s thyroiditis. Endocr Pract. 2013;19(3):479–84. doi:10.4158/EP12376.OR.

Shin DY, Kim KJ, Kim D, Hwang S, Lee EJ. Low serum vitamin D is associated with anti- thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med J. 2014;55(2):476–81. doi: 10.3349/ymj.2014.55.2.476.

Nakashidze I, Ahmad S. Genetic predisposition for pancreatic cancer. In: Ganji PN, Sarfraz A, editors. Theranostic approach for pancreatic cancer. Elsevier; 2019. p. 153–69. doi: 10.1016/B978-0-12-819457-7.00008-6.

Shaikh AP, Khurana R, Shaikh NP, Barua JD, Ali A, Murvanidze I, et al. Peculiarities of some candidate gene polymorphisms in Parkinson’s disease. Pomeranian J Life Sci. 2023;69(2):22-7. doi: 10.21164/pomjlifesci.893.

Nakashidze I, Dariya B, Peshkova T, Beridze S. The genetic polymorphisms in colon cancer. Crit Rev Oncog. 2020;25(4):405–15. doi: 10.1615/CritRevOncog.2020035957.

Nakashidze I, Petrović N, Kedelidze N, Dariya B. Clinical significance of genetic variants in colon cancer. In: Shukla D, Vishvakarma NK, Nagaraju GP, editors. Colon cancer diagnosis and therapy Vol 3. Cham: Springer International Publishing; 2022. p. 69–91. Available from: https://link.springer.com/10.1007/978-3-030- 72702-4_4.

Ahi S, Dehdar MR, Hatami N. Vitamin D deficiency in non-autoimmune hypothyroidism: a case-control study. BMC Endocr Disord. 2020;20(1):41. doi:10.1186/s12902-020-0522-9.

Bizzaro G, Shoenfeld Y. Vitamin D and autoimmune thyroid diseases: facts and unresolved questions. Immunol Res. 2015 ;61(1–2):46–52. doi: 10.1007/s12026-014-8579-z.

Kamyshna II, Pavlovych LB, Malyk IV, Kamyshnyi AM. 25-OH Vitamin D blood serum linkage with VDR gene polymorphism (rs2228570) in thyroid pathology patients in the West-Ukrainian population. J Med Life. 2021;14(4):549–56. doi: 10.25122/jml-2021-0101.

Djurovic J, Stojkovic O, Ozdemir O, Silan F, Akurut C, Todorovic J, et al. Association between FokI , ApaI, and TaqI RFLP polymorphisms in VDR gene and Hashimoto’s thyroiditis: preliminary data from female patients in Serbia. Int J Immunogenet. 2015;42(3):190–4. doi: 10.1111/iji.12199.

Inoue N, Watanabe M, Ishido N, Katsumata Y, Kagawa T, Hidaka Y, et al. The functional polymorphisms of VDR, GC, and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases. Clin Exp Immunol. 2014;178(2):262–9. doi: 10.1111/cei.12420.

Lin WY, Wan L, Tsai CH, Chen RH, Lee CC, Tsai FJ. Vitamin D receptor gene polymorphisms are associated with risk of Hashimoto’s thyroiditis in Chinese patients in Taiwan. J Clin Lab Anal. 2006;20(3):109–12. doi: 10.1002/jcla.20110.

Zarrin R, Bagheri M, Mehdizadeh A, Ayremlou P, Faghfouri AH. The association of FokI and ApaI polymorphisms in vitamin D receptor gene with autoimmune thyroid diseases in the northwest of Iran. Med J Islam Repub Iran. 2018;32:4. doi:10.14196/mjiri.32.4.

Yazici D, Yavuz D, Tarcin O, Sancak S, Deyneli O, Akalin S. Vitamin D receptor gene ApaI, TaqI, FokI and BsmI polymorphisms in a group of Turkish patients with Hashimoto’s thyroiditis. Minerva Endocrinol. 2013;38(2):195–201.

Hanna HWZ, Rizzo C, Abdel Halim RM, El Haddad HE, Salam R, El-Sayed Abou-Youssef H. Vitamin D status in Hashimoto’s thyroiditis and its association with vitamin D receptor genetic variants. J Steroid Biochem Mol Biol. 2021;212:105922. doi: 10.1016/j.jsbmb.2021.105922.

Majid WJ, Abulrazzaq AB, Al-Koofee DAF, Algenabi AHA, Omara AM. The possible role of vitamin D receptor gene polymorphisms and the risk of Hashimoto’s thyroiditis: An Iraqi case-control study. Hum Gene. 2024;39:201239. doi:10.1016/j.humgen.2023.201239 Available online 22 November 2023.

Gao XR, Yu YG. Meta-analysis of the association between vitamin D receptor polymorphisms and the risk of autoimmune thyroid disease. Int J Endocrinol. 2018;2018: 2846943. doi: 10.1155/2018/2846943.

Shaikh AP, Khurana R, Inaishvili M, Shaikh NP, Glonti S, Kedelidze N, et al. VDR Fokl rs2228570 SNP in autoimmune thyroiditis. Transl Clin Med - Georgian Med J. 2022;7(4):10–3.