The Role of Vitamin D Receptor and 25(OH) Vitamin D in Hypothyroidism: Insights from A South Indian Case-Control Study
DOI:
https://doi.org/10.63682/jns.v14i17S.5807Keywords:
VDR, Vitamin D Receptor, ELISA, enzyme-linked immunosorbent assay;, 1,25(OH) D3, 1,25-dihydroxy vitamin D3Abstract
Background: Thyroid hormone disorders are among the most prevalent diseases, significantly impacting public health in India and worldwide. Vitamin D has been associated with modulating thyroid neoplastic and autoimmune diseases, with the vitamin D receptor (VDR) acting as the primary receptor for vitamin D3.
Aim: This study aims to investigate the role of the Vitamin D receptor (VDR) and 25-hydroxyvitamin D (25(OH)D) levels in the pathophysiology of hypothyroidism by exploring their association in a South Indian population through a case-control design.
Methods: An observational study was conducted using a cross-sectional design involving 216 participants (108 hypothyroid and 108 healthy controls), aged 18-70, who were matched for age and sex. Participants with a history of thyroidectomy, pregnant women, and individuals under 18 years were excluded. Blood samples were collected from all participants for necessary investigations. Thyroid profiles, thyroid antibodies, and Vitamin D levels were assessed using a fully automated chemiluminescent hormone analyzer, and VDR levels were measured using a commercially available human ELISA kit. All biochemical parameters were analyzed using a fully automated biochemistry analyzer. A p-value of <0.05 was considered statistically significant.
Results: The VDR levels among cases and controls were 0.72 ± 0.30 and 2.26 ± 0.97, and 25(OH) D3 levels were 17.04 ± 6.03 & 22.09 ± 9.75, respectively. A statistically significant difference in VDR and 25(OH) D3 levels was found between the case and control groups (p < 0.05).
Conclusions: Our findings indicate that serum VDR levels are significantly lower in patients with thyroid abnormalities than in healthy controls, suggesting that VDR may serve as a diagnostic marker for thyroid dysfunction.
Downloads
Metrics
References
Maurya H. Thyroid function disorders among the Indian population. Ann. Thyroid Res. 2018; 4:172-3.
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. Medical journal of the Islamic Republic of Iran. 2018; 32:4.
Dayan, C.M.; Panicker, V. Novel insights into thyroid hormones from the study of common genetic variation. Nat. Rev. Endocrinol. 2009, 5, 211–218. [CrossRef] [PubMed]
Bianco, A.; Kim, B. Deiodinases: Implications of the local control of thyroid hormone action. J. Clin. Invest. 2006, 116, 2571–2579. [CrossRef] [PubMed]
Hoermann, R.; Midgley, J.E.M.; Larisch, R.; Dietrich, J.W. Relational stability in the expression of normality, variation, and control of thyroid function. Front. Endocrinol. 2016, 7, 142. [CrossRef] [PubMed]
Mackawy AM, Al Ayed BM, Al Rashidi BM. Vitamin D deficiency and its association with thyroid disease. Int J Health Sci (Qassim) 2013; 7:267 75.
Tamer G, Arik S, Tamer I, Coksert D. Relative Vitamin D insufficiency in Hashimoto’s thyroiditis. Thyroid 2011; 21:891 6.
Lisse TS, Chun RF, Rieger S, Adams JS, Hewison M. Vitamin D activation of functionally distinct regulatory miRNAs in primary human osteoblasts. J Bone Miner Res. 2013 Jun;28(6):1478-88. doi: 10.1002/jbmr.1882. PMID: 23362149; PMCID: PMC3663893.
Zhou H, Xu C, Gu M. Vitamin D receptor (VDR) gene polymorphisms and Graves’ disease: A meta analysis. Clin Endocrinol (Oxf) 2009; 70:938 45
Drucker, D. J. (2007). The role of gut hormones in glucose homeostasis. J Clin Invest, 117, 24–32.
Shapira Y, Agmon-Levin N, Shoenfeld Y. Geoepidemiology of autoimmune diseases. Autoimmunity 2010; 8: 468–476.
Shoenfeld N, Amital H, Shoenfeld Y. The effect of melanism and vitamin D synthesis on the incidence of autoimmune disease. Nat Clin Pract Rheumatol 2009; 5: 99–105
Wierzbicka A, Oczkowicz M. Sex differences in vitamin D metabolism, serum levels and action. British Journal of Nutrition. 2022;128(11):2115-2130. doi:10.1017/S0007114522000149.
N. Bozkurt, B. Karbek, B. Ucan et al., “e association between severity of vitamin D deficiency and Hashimoto’s thyroiditis,” Endocrine Practice, vol. 19, no. 3, pp. 479–484, 2013.
W. Ke, T. Sun, Y. Zhang et al., “25-Hydroxyvitamin D serum level in Hashimoto’s thyroiditis, but not Grave’sdisease is relatively deficient,” Endocrine Journal, vol. 64, no. 6, pp. 581–587, 2017.
R. Goswami, R. K. Marwaha, N. Gupta et al., “Prevalence of vitamin D deficiency and its relationship with thyroid autoimmunity in Asian Indians: a community-based survey,” British Journal of Nutrition, vol. 102, no. 3, pp. 382–386, 2009.
I. R. Musa, G. I. Gasim, S. Khan, I. A. Ibrahim, H. Aboalazm, and I. Adam, “No association between 25(OH) Vitamin D level and hypothyroidism among females,” Open Access Macedonian Journal of Medical Sciences, vol. 5, no. 2, 2017.
L. Raposo, S. Martins, D. Ferreira, J. T. Guimarães, and A. C. Santos, “Association of vitamin D levels with thyroid function and autoimmunity,” Endocrine Abstracts, vol. 49, p. GP205, 2017.
E. E. Mazokopakis, M. G. Papadomanolaki, K. C. Tsekouras, A. D. Evangelopoulos, D. A. Kotsiris, and A. A. Tzortzinis, “Is vitamin D related to pathogenesis and treatment of Hashimoto’s thyroiditis?” Hellenic journal of nuclear medicine, vol. 18, no. 3, pp. 222–227, 2015.
A. D. Unal, O. Tarcin, H. Parildar, O. Cigerli, H. Eroglu, and N.G.Demirag,“Clinical immunology VitaminDdeficiencyis related to thyroid antibodies in autoimmune thyroiditis,” Central European Journal of Immunology, vol. 39, no. 4, pp. 493–497, 2014.
I. Prasad, R. Kumari, and A. saran, “Vitamin D evaluation in autoimmune thyroid diseases,” International Journal of Contemporary Medical Research, vol. 3, no. 12, 2016.
G. Effraimidis, K. Badenhoop, J. G. P. Tijssen, and W. M. Wiersinga, “Vitamin D deficiency is not associated with early stages of thyroid autoimmunity,” European Journal of Endocrinology, vol. 167, no. 1, pp. 43–48, 2012.
Al-Ghafari AB, Balamash KS, Al Doghaither HA. Serum vitamin D receptor (VDR) levels as a potential diagnostic marker for colorectal cancer. Saudi J Biol Sci. 2020 Mar;27(3):827-832. doi: 10.1016/j.sjbs.2020.01.006. Epub 2020 Jan 21. PMID: 32127758; PMCID: PMC7042625.
Tekeli, Seçkin Özgür, Yağmur Tekeli, Feyza, Erol, Onur, Ellidag, Hamit Yaşar, Eren, Esin and Yılmaz, Necat. "Serum vitamin D receptor levels in gestational diabetes mellitus" Journal of Laboratory Medicine, vol. 42, no. 4, 2018, pp. 149-154. https://doi.org/10.1515/labmed-2017-0149
Bouillon R, Okamura WH, Norman AW. Structure-function relationships in the vitamin D endocrine system. Endocr Rev 1995; 16:200–57.
Nguyen M, Trubert CL, Rizk-Rabin M, Rehan VK, Besancon F, Cayre YE, et al. 1,25-Dihydroxyvitamin D3 and fetal lung maturation: immunogold detection of VDR expression in pneumocytes type II cells and effect on fructose 1,6 bisphosphatase. J Steroid Biochem Mol Biol 2004; 89:90–3.
Menezes RJ, Cheney RT, Husain A, Tretiakova M, Loewen G, Johnson CS, et al. Vitamin D receptor expression in normal, premalignant, and malignant human lung tissue. Cancer Epidemiol Biomarkers Prev 2008; 17:1104–10.
Lin R, Nagai Y, Sladek R, Bastien Y, Ho J, Petrecca K, et al. Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol 2002; 16:1243–56.
Wood RJ, Tchack L, Angelo G, Pratt RE, Sonna LA. DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line. Physiol Genomics 2004; 17:122–9.
Wang TT, Tavera-Mendoza LE, Laperriere D, Libby E, MacLeod NB, Nagai Y, et al. Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol 2005; 19:2685–95.
Dusso AS, Brown AJ, Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol 2005;289: F8–28.
Van Cromphaut SJ, et al. Duodenal calcium absorption in vitamin D receptor-knockout mice: functional and molecular aspects. Proc Natl Acad Sci USA. 2001; 98:13324–13329. [PubMed: 11687634]
Song Y, et al. Vitamin D receptor (VDR) knockout mice reveal VDR-independent regulation of intestinal calcium absorption and ECaC2 and calbindin D9k mRNA. J Nutr. 2003; 133:374–80. [PubMed: 12566470]
Wang Y, et al. The vitamin D receptor in the proximal renal tubule is a key regulator of serum 1alpha,25-dihydroxyvitamin D3. Am J Physiol Endocrinol Metab. 2015; 308: E201–5. [PubMed: 25425001]
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
