Hypothyroidism induced by excessive-iodine is associated in humans with altered hsa-miR-199a-5p/HIF-1α axis and thyroglobulin.

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.