Prediction of the cognitive impairment development in patients with autoimmune thyroiditis and hypothyroidism.

Objective. The aim of the present work is to define the risk factors that can affect the presence of a cognitive impairment and analyze the associations of the brain-derived neurotrophic factor (BDNF) gene polymorphism (rs6265), vitamin D receptor (VDR) gene polymorphism (rs2228570), and N-methyl-D-aspartate (NMDA) receptor gene polymorphism (rs4880213) with the cognitive impairment in patients with autoimmune thyroiditis and hypothyroidism in the Western Ukraine population and predict the development of cognitive disorders in these patients. Methods. The study involved 153 patients with various forms of thyroid pathology (hypothyroidism, autoimmune thyroiditis, elevated serum antibodies anti-thyroglobulin and anti-thyroid peroxidase). Cognitive impairment in the examined patients was evaluated based on the results of the Mini-Mental State Examination (MMSE) test. BDNF, GRIN2B, and 25-OH Vitamin D levels in the serum of the patients and healthy individuals were quantified using highly sensitive commercial enzyme-linked immunosorbent assay kits. Genotyping of the VDR (rs2228570), BDNF (rs6265), and NMDA receptor (rs4880213) gene polymorphism was performed using TaqMan probes and Taq-Man Genotyping Master Mix (4371355) on CFX96™Real-Time PCR Detection System. Polymerase chain reaction (PCR) for TaqMan genotyping was carried out according to the kit instructions. Results. Strong direct relationship between the "Level GRIN2B" and cognitive impairments (p=0.006) was established after evaluating the complex model based on the values of the regression coefficient. An increase in the likelihood of cognitive impairment by 24.898-fold (p=0.012) was seen after assessing the effect of the CT rs6265 genotype. In addition, direct relationship between the influence of the TT rs6265 genotype and an increase in the likelihood of cognitive impairment by a factor of 21.734 (p=0.024) was also established. Conclusion. The present data indicate that the BDNF, TSH, fT4, and vitamin D levels prognostically belong to the significant indicators of the cognitive impairment development.

BDNF blood serum linkage with BDNF gene polymorphism (rs6265) in thyroid pathology patients in the West-Ukrainian population.

Objective. Brain-derived neurotrophic factor (BDNF) is identified as an important growth factor involved in learning and memory. Patients with Hashimoto's thyroiditis can suffer from cognitive dysfunction, whereas BDNF is directly regulated by thyroid hormones. It seems reasonable to propose that changes in BDNF expression underlie some of the persistent neurological impairments associated with hypothyroidism. Methods. The study involved a total of 153 patients with various forms of thyroid pathology. BDNF levels in the sera of the patients and healthy individuals were quantified using enzyme-linked immunosorbent assay with highly sensitive Human BDNF ELISA Kit. Genotyping of the BDNF (rs6265) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) on CFX96™Real-Time PCR Detection System. Polymerase chain reaction (PCR) for TaqMan genotyping was carried out according to the kit instructions. Results. Distribution rs6265 variants in the patients depending on the different types of thyroid pathology showed no significant difference in the relative frequency of BDNF polymorphic variants. Presence of hypothyroidism, regardless of its cause (autoimmune or postoperative), there was a decrease in the serum BDNF levels in all genotypes carriers compared with the control group. The analysis of the correlation between BDNF levels and the levels of thyroid-stimulating hormone (TSH), thyroxine (T4), anti-thyroglobulin (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibodies showed a significant inverse relationship between BDNF and TSH levels (p<0.001), a direct correlation between BDNF and T4 levels in the blood (p<0.001), and a weak direct relationship between anti-Tg and BDNF levels (p=0.0157). Conclusion. The C allele presence is protective and associates with the lowest chances for reduced serum BDNF levels in thyroid pathology patients in the West-Ukrainian population. However, the T-allele increases the risk of low BDNF levels almost 10 times in observed subjects.