Vitamin D Level and Vitamin D Receptor Gene Polymorphisms in Iranian Azeri Turkish Patients With Autoimmune Thyroid Diseases
The Autoimmune thyroid diseases (AITDs) are among the most common endocrine disorders. Vitamin D as an immunomodulator and Vitamin D receptor (VDR) gene polymorphisms may be effective in AITDs pathogenesis. The aim of this study was to evaluate the vitamin D level and VDR BsmI and TaqI polymorphisms in Iranian Azeri Turkish patients with AITDs. This case-control study included 121 adults with AITDs and 117 non-AITDs controls. Serum level of 25-hydroxyvitamin D was measured by electrochemiluminescence (ECL) immunoassay. BsmI and TaqI polymorphisms were assessed by polymerase chain reaction fragment length polymorphism technique. The serum level of 25-hydroxyvitamin D in AITDs patients were lower than controls (P=0.03). The frequencies of TT, TC, CC, T and C genotypes/alleles at TaqI (rs731236) marker were 52.1%, 34.7%, 13.2% , 69.4% and 30.6% in AITDs and 44.4%, 41.9%, 13.7%, 65.4% and 34.6% in controls, respectively. The frequencies of AA, AG, GG, A and G genotypes/alleles at BsmI (rs1544410) marker were 14%, 64.5%, 21.5% , 46.3% and 53.7% in AITDs and 26.5%, 58.1%, 15.4%, 55.6% and 44.4% in controls, respectively. BsmI (rs1544410) GG+AG genotypes and G allele were more frequent among patients with Hashimoto compared with control group (86.6% vs. 73.5% (OR: 2.34, 95% CI: 1.16-4.70, P = 0.014) and 54.29% vs. 44.44% (OR: 1.48, 95% CI: 1.02-2.15, P = 0.038), respectively). Vitamin D status can be related to AITDs pathogenesis. BsmI (rs1544410) GG+AG genotypes and G allele may play an important role in the predisposition to Hashimoto.
Vanderpump MP. The epidemiology of thyroid disease. Br Med Bull 2011;99:39-51.
Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Autoimmun Rev 2015;14:174-80.
McGrogan A, Seaman HE, Wright JW, de Vries CS. The incidence of autoimmune thyroid disease: a systematic review of the literature. Clin Endocrinol (Oxf) 2008;69:687-96.
Guarneri F, Benvenga S. Environmental factors and genetic background that interact to cause autoimmune thyroid disease. Curr Opin Endocrinol Diabetes Obes 2007;14:398-409.
Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. High vitamin D status in younger individuals is associated with low circulating thyrotropin. Thyroid 2013;23:25–30.
Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 1998;13:325-49.
Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 2006;371:1-12.
Bhanushali AA, Lajpal N, Kulkarni SS, Chavan SS, Bagadi SS, Das BR. Frequency of fokI and taqI polymorphism of vitamin D receptor gene in Indian population and its association with 25-hydroxyvitamin D levels. Indian J Hum Genet 2009;15:108-13.
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;178:262-9.
Ma J, Wu D, Li C, Fan C, Chao N, Liu J, et al. Lower Serum 25-Hydroxyvitamin D Level is Associated With 3 Types of Autoimmune Thyroid Diseases. Medicine (Baltimore) 2015;94:e1639.
Li K, Shi Q, Yang L, Li X, Liu L, Wang L, et al. The association of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels with generalized vitiligo. Br J Dermatol 2012;167:815-21.
Emerah AA, El-Shal AS. Role of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D level in Egyptian female patients with systemic lupus erythematosus. Mol Biol Rep 2013;40:6151-62.
Guleryuz B, Akin F, Tunc Ata M, Mergen Dalyanoglu M, Turgut S. Vitamin-D Receptor (VDR) Gene Polymorphisms (TaqI, FokI) in Turkish Patients with Hashimoto’s Thyroiditis: Relationship to the levels of Vit-D and Cytokines. Endocr Metab Immune Disord Drug Targets 2016;16:131-9.
Giovinazzo S, Vicchio TM, Certo R, Alibrandi A, Palmieri O, Campenni A, et al. Vitamin D receptor gene polymorphisms/haplotypes and serum 25(OH)D3 levels in Hashimoto's thyroiditis. Endocrine 2017;55:599-606.
Ramos-Lopez E, Kurylowicz A, Bednarczuk T, Paunkovic J, Seidl C, Badenhoop K. Vitamin D receptor polymorphisms are associated with Graves' disease in German and Polish but not in Serbian patients. Thyroid 2005;15:1125-30.
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;38:195-201.
Mansournia N, Mansournia MA, Saeedi S, Dehghan J. The association between serum 25OHD levels and hypothyroid Hashimoto's thyroiditis. J Endocrinol Invest 2014;37:473-6.
Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev 2014;13:391-7.
Ginsberg J. Diagnosis and management of Graves' disease. CMAJ 2003;168:575-85.
Menon B, Harinarayan CV. The effect of anti epileptic drug therapy on serum 25-hydroxyvitamin D and parameters of calcium and bone metabolism--a longitudinal study. Seizure 2010;19:153-8.
Pappa HM, Bern E, Kamin D, Grand RJ. Vitamin D status in gastrointestinal and liver disease. Curr Opin Gastroenterol 2008;24:176-83.
Williams S, Malatesta K, Norris K. Vitamin D and chronic kidney disease. Ethn Dis 2009;19:S5-8-11.
Kennel KA, Drake MT. Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc 2009;84:632-8.
Abd El Gawad SS, Abdul Samee ER, Metwali AA, Abd El Gawad MS. Vitamin D receptor gene polymorphism and its association with 1,25-dihydroxyvitamin D(3) in patients with Graves disease in an Egyptian population: a pilot study. Endocr Pract 2012;18:132-9.
Gandini S, Gnagnarella P, Serrano D, Pasquali E, Raimondi S. Vitamin D receptor polymorphisms and cancer. Adv Exp Med Biol 2014;810:69-105.
Jia F, Sun RF, Li QH, Wang DX, Zhao F, Li JM, et al. Vitamin D receptor BsmI polymorphism and osteoporosis risk: a meta-analysis from 26 studies. Genet Test Mol Biomarkers 2013;17:30-4.
Wei S, Baloch ZW, LiVolsi VA. Parathyroid adenoma in patients with Graves' disease: a report of 21 cases. Endocr Pathol 2015;26:71-4.
Muscogiuri G, Tirabassi G, Bizzaro G, Orio F, Paschou SA, Vryonidou A, et al. Vitamin D and thyroid disease: to D or not to D? Eur J Clin Nutr 2015;69:291-6.
Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Danko K, et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol 2011;8:243-7.
Choi YM, Kim WG, Kim TY, Bae SJ, Kim HK, Jang EK, et al. Low levels of serum vitamin D3 are associated with autoimmune thyroid disease in pre-menopausal women. Thyroid 2014;24:655-61.
Huang J, Xie ZF. Polymorphisms in the vitamin D receptor gene and multiple sclerosis risk: a meta-analysis of case-control studies. J Neurol Sci 2012;313:79-85.
Kamel MM, Fouad SA, Salaheldin O, El-Razek Ael R, El-Fatah AI. Impact of vitamin D receptor gene polymorphisms in pathogenesis of Type-1 diabetes mellitus. Int J Clin Exp Med 2014;7:5505-10.
Wang L, Wang ZT, Hu JJ, Fan R, Zhou J, Zhong J. Polymorphisms of the vitamin D receptor gene and the risk of inflammatory bowel disease: a meta-analysis. Genet Mol Res 2014;13:2598-610.
Shimada A, Kanazawa Y, Motohashi Y, Yamada S, Maruyama T, Ikegami H, et al. Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese. J Autoimmun 2008;30:207-11.
Agliardi C, Guerini FR, Saresella M, Caputo D, Leone MA, Zanzottera M, et al. Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB1*15-positive individuals. Brain Behav Immun 2011;25:1460-7.
Maalej A, Petit-Teixeira E, Chabchoub G, Hamad MB, Rebai A, Farid NR, et al. Lack of association of VDR gene polymorphisms with thyroid autoimmune disorders: familial and case/control studies. J Clin Immunol 2008;28:21-5.
Stefanic M, Papic S, Suver M, Glavas-Obrovac L, Karner I. Association of vitamin D receptor gene 3'-variants with Hashimoto's thyroiditis in the Croatian population. Int J Immunogenet 2008;35:125-31.
Feng M, Li H, Chen SF, Li WF, Zhang FB. Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine 2013;43:318-26.
Smolders J, Peelen E, Thewissen M, Menheere P, Tervaert JW, Hupperts R, et al. The relevance of vitamin D receptor gene polymorphisms for vitamin D research in multiple sclerosis. Autoimmun Rev 2009;8:621-6.
Smolders J, Damoiseaux J, Menheere P, Tervaert JW, Hupperts R. Fok-I vitamin D receptor gene polymorphism (rs10735810) and vitamin D metabolism in multiple sclerosis. J Neuroimmunol 2009;207:117-21.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.