He Jing, Dong Yishan, Chen Xianglan, Wang Shuo, Shen Zheng, Huang Xu, Li Weijia, Yang Zhihan, Cheng Jin, Li Jinyu, Liu Qiaoling, Xu Ziqi, Sun Dianjun, Zhang Wei
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health, Harbin, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, China.
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health, Harbin, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, China; Guangdong Provincial People's Hospital Zhuhai Hospital, Zhuhai, Guangdong, China.
J Nutr Biochem. 2025 Apr;138:109841. doi: 10.1016/j.jnutbio.2025.109841. Epub 2025 Jan 11.
The adverse effect of excessive iodine intake has attracted extensive attention. However, the role of excessive iodine on hypothyroidism and detailed mechanism are not exactly known. Studies have shown that miRNAs are crucial to the occurrence and development of hypothyroidism. Nevertheless, there still limited population-based studies on the miRNA-mRNA regulation in the occurrence of hypothyroidism induced by excessive iodine. Total of 291 hypothyroidism patients and 291 controls matched by sex (1:1) and age (±3 years) were enrolled from Heze City, Shandong Province. Multiple logistic regression analysis revealed that water iodine concentration of 100-300 µg/L was an independent risk factor for hypothyroidism. Additionally, excessive water iodine was associated with an increase in thyroglobulin (Tg) concentration in new diagnosed hypothyroidism patients. Further, high-throughput miRNA sequencing indicated that hsa-miR-19b-3p, hsa-miR-199a-5p, hsa-miR-204-5p and hsa-miR-144-3p were significantly correlated with the occurrence of hypothyroidism. Q-PCR results showed that levels of hsa-miR-199a-5p and hsa-miR-204-5p in the hypothyroidism group were markedly lower than those in the control group. In addition, among the hypothyroidism patients, hsa-miR-199a-5p level in water iodine >100 µg/L group was remarkably higher than that in 10-100 µg/L group. Furthermore, HIF-1α and PD-L1 mRNA levels in whole blood were determined, which are the target genes regulated by miRNA-199a-5p in previous studies. Compared with the control group, HIF-1α mRNA level was significantly increased in the hypothyroidism group. In the hypothyroidism case group, compared with the 10-100 µg/L group, HIF-1α mRNA level was remarkably decreased in water iodine >100 µg/L group. Collectively, miR-199a-5p/HIF-1α axis may contribute to hypothyroidism induced by excessive iodine through thyroglobulin.
碘摄入过量的不良影响已引起广泛关注。然而，过量碘对甲状腺功能减退的作用及具体机制尚不完全清楚。研究表明，微小RNA（miRNAs）对甲状腺功能减退的发生和发展至关重要。然而，关于过量碘所致甲状腺功能减退发生过程中miRNA-信使核糖核酸（mRNA）调控的基于人群的研究仍然有限。从山东省菏泽市招募了291例甲状腺功能减退患者和291例按性别（1:1）和年龄（±3岁）匹配的对照。多因素逻辑回归分析显示，水碘浓度为100 - 300μg/L是甲状腺功能减退的独立危险因素。此外，过量的水碘与新诊断的甲状腺功能减退患者甲状腺球蛋白（Tg）浓度升高有关。进一步的高通量miRNA测序表明，hsa-miR-19b-3p、hsa-miR-199a-5p、hsa-miR-204-5p和hsa-miR-144-3p与甲状腺功能减退的发生显著相关。定量聚合酶链反应（Q-PCR）结果显示，甲状腺功能减退组中hsa-miR-199a-5p和hsa-miR-204-5p的水平明显低于对照组。此外，在甲状腺功能减退患者中，水碘>100μg/L组的hsa-miR-199a-5p水平显著高于10 - 100μg/L组。此外，还测定了全血中缺氧诱导因子-1α（HIF-1α）和程序性死亡配体1（PD-L1）的mRNA水平，它们是先前研究中受miRNA-199a-5p调控的靶基因。与对照组相比，甲状腺功能减退组的HIF-1α mRNA水平显著升高。在甲状腺功能减退病例组中，与10 - 100μg/L组相比，水碘>100μg/L组的HIF-1α mRNA水平显著降低。总的来说，miR-199a-5p/HIF-1α轴可能通过甲状腺球蛋白导致过量碘所致的甲状腺功能减退。
