Association between Serum Brain-derived Neurotrophic Factor and 25-OH Vitamin D Levels with Vitamin D Receptors Gene Polymorphism (rs2228570) in Patients with Autoimmune Thyroiditis and Hypothyroidism
DOI:
https://doi.org/10.3889/oamjms.2021.6631Keywords:
Vitamin D receptors, Brain-derived neurotrophic factor, 25-OH Vitamin D, rs2228570, Autoimmune thyroiditis, HypothyroidismAbstract
BACKGROUND: Different polymorphisms in Vitamin D receptors (VDRs) have an important role in autoimmune thyroiditis (AIT) risk. Hashimoto’s thyroiditis (HT) is the most recurrent autoimmune thyroid disorder. Patients with HT may suffer from cognitive impairment brain-derived neurotrophic factor (BDNF) which has been identified as an important growth factor that is involved in learning and memory.
AIM: This study examined the linkage of VDR gene polymorphism (rs2228570) with blood serum levels of BDNF and 25-OH Vitamin D in thyroid pathology of patients in the West Ukrainian population.
METHODS: This research is a case–control study was performed in HSEEU “Bukovinian State Medical University,” Chernivtsi Regional Endocrinology Center, and I. Horbachevsky Ternopil National Medical University, Ukraine, from September 2017 to December 2020. The study involved a total of 153 patients with post-operative hypothyroidism, hypothyroidism induced by AIT, and patients with both AIT and elevated serum antibodies anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase. BDNF levels in the sera of the patients and healthy individuals were quantified using enzyme-linked immunosorbent assay (ELISA) with highly sensitive Human BDNF ELISA Kit. Genotyping of the VDR (rs2228570) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) on CFX96™ Real-Time Polymerase Chain Reaction (PCR) Detection System (Bio-Rad Laboratories, Inc., USA). PCR for TaqMan genotyping was carried out according to the kit instructions (Applied Biosystems, USA).
RESULTS: Our study revealed a significant decrease in the BDNF level in the study group in carriers of the AA and AG genotypes by 1.58 and 2.39 times, corresponding, compared with carriers of the AA genotype in the control group. Concurrently, there was no significant difference in the BDNF level between different genotypes of VDR rs2228570 in the research group. In our study, analysis of the correlation between serum BDNF levels and 25-OH Vitamin D concentration shows a moderate direct relationship (r = 0.4) between BDNF and 25-OH Vitamin D (p = 0.006).
CONCLUSIONS: The rs2228570 VDR polymorphism is not a risk factor for decreased serum BDNF levels. At the same time, our study found a moderate direct relationship between serum BDNF levels and 25-OH Vitamin D.Downloads
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Tillmann FP, Harth A, Jörres A. Hashimoto’s thyroiditis-associated acute renal failure and pitfalls of eGFR interpretation in thyroid diseases. Eur J Case Rep Intern Med. 2021;8(7):002645. https://doi.org/10.12890/2021_002645 PMid:34268270 DOI: https://doi.org/10.12890/2021_002645
Krysiak R, Kowalcze K, Okopień B. The impact of exogenous Vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and early-onset androgenic alopecia. Pharmacol Rep. 2021. https://doi.org/10.1007/s43440-021-00295-3 PMid:34106452 DOI: https://doi.org/10.1007/s43440-021-00295-3
Zhou F, Liang Z, Wang X, Tan G, Wei W, Zheng G, et al. The VDR gene confers a genetic predisposition to Graves’ disease and Graves’ ophthalmopathy in the Southwest Chinese Han population. Gene. 2021;793:145750. https://doi.org/10.1016/j.gene.2021.145750 PMid:34077777 DOI: https://doi.org/10.1016/j.gene.2021.145750
Valencia-Sanchez C, Pittock SJ, Mead-Harvey C, Dubey D, Flanagan EP, Lopez-Chiriboga S, et al. Brain dysfunction and thyroid antibodies: Autoimmune diagnosis and misdiagnosis. Brain Commun. 2021;3(2):fcaa233. https://doi.org/10.1093/braincomms/fcaa233 PMid:34061124 DOI: https://doi.org/10.1093/braincomms/fcaa233
Sable HJ, MacDonnchadh JJ, Lee HW, Butawan M, Simpson RN, Krueger KM, Bloomer RJ. Working memory and hippocampal expression of BDNF, ARC, and P-STAT3 in rats: Effects of diet and exercise. Nutr Neurosci. 2021.1-14. https://doi.org/10.1080/1028415x.2021.1885230 PMid:33593241 DOI: https://doi.org/10.1080/1028415X.2021.1885230
Hung PL, Hsu MH, Yu HR, Wu KL, Wang FS. Thyroxin protects white matter from hypoxic-ischemic insult in the immature Sprague-Dawley rat brain by regulating periventricular white matter and cortex BDNF and CREB pathways. Int J Mol Sci. 2018;19(9):2573. https://doi.org/10.3390/ijms19092573 PMid:30158497 DOI: https://doi.org/10.3390/ijms19092573
Puhlmann LM, Linz R, Valk SL, Vrticka P, de Wael RV, Bernasconi A, et al. Association between hippocampal structure and serum brain-derived neurotrophic factor (BDNF) in healthy adults: A registered report. Neuroimage. 2021;236:118011. https://doi.org/10.1016/j.neuroimage.2021.118011 PMid:33852941 DOI: https://doi.org/10.1016/j.neuroimage.2021.118011
Xiong LL, Chen J, Du RL, Liu J, Chen YJ, Hawwas MA, et al. Brain-derived neurotrophic factor and its related enzymes and receptors play important roles after hypoxic-ischemic brain damage. Neural Regen Res. 2021;16(8):1453-9. https://doi.org/10.4103/1673-5374.303033 PMid:33433458 DOI: https://doi.org/10.4103/1673-5374.303033
Peters RB, Xavier J, Mondin TC, Cardoso TA, Ferreira FB, Teixeira L, et al. BDNF Val66Met polymorphism and resilience in major depressive disorder: The impact of cognitive psychotherapy. Braz J Psychiatry. 2021;43:22-8. https://doi.org/10.1590/1516-4446-2019-0726 PMid:32844885 DOI: https://doi.org/10.1590/1516-4446-2019-0726
Bilous I, Pavlovych L, Krynytska I, Marushchak M, Kamyshnyi A. Apoptosis and cell cycle pathway-focused genes expression analysis in patients with different forms of thyroid pathology. Open Access Maced J Med Sci. 2020;8(B):784-92. https://doi.org/10.3889/oamjms.2020.4760 DOI: https://doi.org/10.3889/oamjms.2020.4760
Bilous II, Korda MM, Krynytska IY, Kamyshnyi AM. Nerve impulse transmission pathway-focused genes expression analysis in patients with primary hypothyroidism and autoimmune thyroiditis. Endocr Regul. 2020;54(2):109-18. https://doi.org/10.2478/enr-2020-0013 PMid:32597152 DOI: https://doi.org/10.2478/enr-2020-0013
Bilous II, Pavlovych LL, Kamyshnyi AM. Primary hypothyroidism and autoimmune thyroiditis alter the transcriptional activity of genes regulating neurogenesis in the blood of patients. Endocr Regul. 2021;55(1):5-15. https://doi.org/10.2478/enr-2021-0002 PMid:33600668 DOI: https://doi.org/10.2478/enr-2021-0002
Kamyshna II, Pavlovych LB, Maslyanko VA, Kamyshnyi AM. Analysis of the transcriptional activity of genes of neuropeptides and their receptors in the blood of patients with thyroid pathology. J Med Life. 2021;14(2):243-9. PMid:34104248
Kamyshna I, Kamyshnyi A. Transcriptional activity of neurotrophins genes and their receptors in the peripheral blood in patients with thyroid diseases in Bukovinian population of Ukraine. Open Access Maced J Med Sci. 2021;9(A):208-16. https://doi.org/10.3889/oamjms.2021.6037 DOI: https://doi.org/10.3889/oamjms.2021.6037
Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American association of clinical endocrinologists and the American thyroid association. Endocr Pract. 2012;18(6):988-1028. https://doi.org/10.4158/ep12280.gl PMid:23246686 DOI: https://doi.org/10.4158/EP12280.GL
Sonoyama T, Stadler LKJ, Zhu M, Keogh JM, Henning E, Hisama F, et al. Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities. Sci Rep. 2020;10(1):9028. https://doi.org/10.1038/s41598-020-65531-x PMid:32493978 DOI: https://doi.org/10.1038/s41598-020-65531-x
Shabani S, Farbood Y, Mard SA, Sarkaki A, Ahangarpour A, Khorsandi L. The regulation of pituitary-thyroid abnormalities by peripheral administration of levothyroxine increased brain-derived neurotrophic factor and reelin protein expression in an animal model of Alzheimer’s disease. Can J Physiol Pharmacol. 2018;96(3):275-80. https://doi.org/10.1139/cjpp-2016-0434 PMid:28846851 DOI: https://doi.org/10.1139/cjpp-2016-0434
Degen AS, Krynytska IY, Kamyshnyi AM. Changes in the transcriptional activity of the entero-insular axis genes in streptozotocin-induced diabetes and after the administration of TNF-α _non-selective blockers. Endocr Regul. 2020;54(3):160-71. https://doi.org/10.2478/enr-2020-0019 PMid:32857721 DOI: https://doi.org/10.2478/enr-2020-0019
Putilin DA, Evchenko SY, Fedoniuk LY, Tokarskyy OS, Kamyshny OM, Migenko LM, et al. The influence of metformin to the transcriptional activity of the mTOR and FOX3 genes in parapancreatic adipose tissue of streptozotocin-induced diabetic rats. J Med Life. 2020;13(1):50-5. https://doi.org/10.1530/endoabs.49.ep455 PMid:32341701 DOI: https://doi.org/10.1530/endoabs.49.EP455
Lyubomirskaya ES, Kamyshnyi AM, Krut YY, Smiianov VA, Fedoniuk LY, Romanyuk LB, et al. SNPs and transcriptional activity of genes of innate and adaptive immunity at the maternal-fetal interface in woman with preterm labour, associated with preterm premature rupture of membranes. Wiad Lek. 2020;73(1):25-30. https://doi.org/10.14739/2310-1237.2018.2.141400 PMid:32124801 DOI: https://doi.org/10.14739/2310-1237.2018.2.141400
Lyubomirskaya K, Krut Y, Sergeyeva L, Khmil S, Lototska O, Petrenko N, et al. Preterm premature rupture of membranes: Prediction of risks in women of Zaporizhzhia region of Ukraine. Pol Merkur Lekarski. 2020;48(288):399-405. PMid:33387426
Dzhuryak V, Sydorchuk L, Sydorchuk A, Kamyshnyi O, Kshanovska A, Levytska S, et al. The cytochrome 11B2 aldosterone synthase gene CYP11B2 (RS1799998) polymorphism associates with chronic kidney disease in hypertensive patients. Biointerface Res Appl Chem. 2020;10(3):5406-11. https://doi.org/10.33263/briac103.406411 DOI: https://doi.org/10.33263/BRIAC103.406411
Kim D. The role of Vitamin D in thyroid diseases. Int J Mol Sci. 2017;18(9):1949. PMid:28895880 DOI: https://doi.org/10.3390/ijms18091949
Goltz A, Janowitz D, Hannemann A, Nauck M, Hoffmann J, Seyfart T, et al. Association of brain-derived neurotrophic factor and Vitamin D with depression and obesity: A population-based study. Neuropsychobiology. 2017;76(4):171-81. https://doi.org/10.1159/000489864 PMid:29920493 DOI: https://doi.org/10.1159/000489864
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Copyright (c) 2021 Iryna Kamyshna, Larysa Pavlovych, Aleksandr Kamyshnyi (Author)
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