Duan Xiping, Zhang Tianchi, Wang Ke
Acupuncture Anaesthesia Clinical Research Institute, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Front Endocrinol (Lausanne). 2024 Nov 27;15:1436823. doi: 10.3389/fendo.2024.1436823. eCollection 2024.
Metabolic disorders are significant risk factors for peripheral neuropathy (PN) diseases. However, current clinical observational studies cannot fully determine the causal relationships between hypothyroidism (HT) and PN diseases.
We performed univariate Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) associated with hypothyroidism and two diseases clinically presented as HT (autoimmune thyroid disease and benign neoplasm of the pituitary gland and craniopharyngeal duct) as instrumental variables. We selected eight peripheral neuropathy diseases (diabetic neuropathy, nerve root/plexus disorder, carpal tunnel syndrome, polyneuropathies, sciatica with lumbago, trigeminal neuralgia, postherpetic neuralgia, small fiber neuropathy) as outcomes. Genetic data were sourced from authoritative genome-wide association study (GWAS) datasets. We primarily used the inverse variance-weighted (IVW) method and conducted a comprehensive sensitivity analysis to ensure robustness.
The IVW results indicated that HT was significantly associated with an increased risk of diabetic peripheral neuropathy (OR = 1.22, = 6.49E-05). HT was also significantly linked to nerve root/plexus disorder (OR = 1.04, p = 6.43E-06) and carpal tunnel syndrome (OR = 1.04, = 0.004), but appeared to be a potential protective factor for polyneuropathies (OR = 0.93, = 0.0009). Additionally, autoimmune thyroid disease (AITD) was identified as a potential risk factor for carpal tunnel syndrome (OR = 13.79, = 0.006) and a protective factor for polyneuropathies (OR = 0.0011; = 4.44E-5).
This study provides genetic evidence supporting potential causal links between hypothyroidism and various peripheral neuropathy diseases.
代谢紊乱是周围神经病变（PN）疾病的重要危险因素。然而，目前的临床观察性研究尚不能完全确定甲状腺功能减退症（HT）与PN疾病之间的因果关系。
我们使用与甲状腺功能减退症以及临床上表现为HT的两种疾病（自身免疫性甲状腺疾病和垂体及颅咽管良性肿瘤）相关的单核苷酸多态性（SNP）进行单变量孟德尔随机化（MR）分析，将其作为工具变量。我们选择了八种周围神经病变疾病（糖尿病性神经病变、神经根/神经丛疾病、腕管综合征、多发性神经病、坐骨神经痛伴腰痛、三叉神经痛、带状疱疹后神经痛、小纤维神经病变）作为研究结果。遗传数据来源于权威的全基因组关联研究（GWAS）数据集。我们主要使用逆方差加权（IVW）方法，并进行了全面的敏感性分析以确保结果的稳健性。
IVW结果表明，HT与糖尿病周围神经病变风险增加显著相关（OR = 1.22，= 6.49E - 05）。HT还与神经根/神经丛疾病（OR = 1.04，p = 6.43E - 06）和腕管综合征（OR = 1.04，= 0.004）显著相关，但似乎是多发性神经病的潜在保护因素（OR = 0.93，= 0.0009）。此外，自身免疫性甲状腺疾病（AITD）被确定为腕管综合征的潜在危险因素（OR = 13.79，= 0.006）和多发性神经病的保护因素（OR = 0.0011；= 4.44E - 5）。
本研究提供了遗传证据，支持甲状腺功能减退症与各种周围神经病变疾病之间存在潜在因果关系。
