DNA methylation of genes that mediate autophagosome formation contributes to iodine-induced autoimmune thyroiditis: A population-based study conducted at regions with different iodine levels in China.

PURPOSE: Autoimmune thyroiditis (AIT) results from a combination of genetic predispositions and environmental factors. This study aims to examine the methylation patterns of genes that mediate autophagosome formation (MAF) between AIT patients and controls from areas with different water iodine levels.

METHODS

A protein-protein interaction (PPI) network was constructed to explore the interactions of autophagy-related genes (ARGs). The MCODE plugin in Cytoscape software identified two functional epigenetic modules. We included 176 AIT cases from regions with varying water iodine concentrations and matched controls at a 1:1 ratio. The MethylTarget™ assay was employed to assess DNA methylation changes in six MAF-related genes and analyzed the association between iodine levels and epigenetic modifications.

RESULTS

Significant methylation differences were observed in 11 targets with 75 CpG sites on MAF-related genes between AIT patients and controls (P < 0.05). Methylation levels were generally lower in AIT patients. A negative correlation was found between the methylation status of PRKAB1_36 and urinary iodine concentration (UIC) (rs = -0.208, P = 0.006). In iodine-fortification areas (IFA), AIT patients exhibited significantly higher mRNA expression levels of six MAF-related genes in whole blood compared to controls (P < 0.05).

CONCLUSION

Environmental water iodine concentration influences the DNA methylation status of MAF-related genes. Hypomethylated targets and sites in these genes were identified, and the relative mRNA expression levels of these genes were significantly increased in AIT cases from regions with a history of prolonged iodine deficiency followed by iodine supplementation.