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

Abstract

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.