I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine.
HSEEU "Bukovinian State Medical University", Chernivtsi, Ukraine.
Endocr Regul. 2022 Jul 13;56(3):178-189. doi: 10.2478/enr-2022-0019.
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. 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. 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. The present data indicate that the BDNF, TSH, fT4, and vitamin D levels prognostically belong to the significant indicators of the cognitive impairment development.
本研究旨在确定可能影响认知障碍存在的风险因素，并分析脑源性神经营养因子（BDNF）基因多态性（rs6265）、维生素 D 受体（VDR）基因多态性（rs2228570）和 N-甲基-D-天冬氨酸（NMDA）受体基因多态性（rs4880213）与乌克兰西部人群自身免疫性甲状腺炎和甲状腺功能减退患者认知障碍的相关性，并预测这些患者认知障碍的发展。该研究纳入了 153 名患有各种甲状腺疾病（甲状腺功能减退症、自身免疫性甲状腺炎、血清抗甲状腺球蛋白和抗甲状腺过氧化物酶抗体升高）的患者。通过 Mini-Mental State Examination（MMSE）测试评估了检查患者的认知障碍。使用高敏商业酶联免疫吸附测定试剂盒定量测定了患者和健康个体血清中的 BDNF、GRIN2B 和 25-OH 维生素 D 水平。使用 TaqMan 探针和 Taq-Man 基因分型主混合物（4371355）在 CFX96™实时 PCR 检测系统上对 VDR（rs2228570）、BDNF（rs6265）和 NMDA 受体（rs4880213）基因多态性进行基因分型。TaqMan 基因分型的聚合酶链反应（PCR）按照试剂盒说明进行。在评估基于回归系数值的复杂模型后，确定“GRIN2B 水平”与认知障碍之间存在强烈的直接关系（p=0.006）。在评估 CT rs6265 基因型的作用后，发现认知障碍的可能性增加了 24.898 倍（p=0.012）。此外，还确定了 TT rs6265 基因型的影响与认知障碍可能性增加 21.734 倍之间存在直接关系（p=0.024）。目前的数据表明，BDNF、TSH、fT4 和维生素 D 水平从预后上属于认知障碍发展的重要指标。
