The Whole Blood DNA Methylation Patterns of Extrinsic Apoptotic Signaling Pathway Related Genes in Autoimmune Thyroiditis among Areas with Different Iodine Levels.

Abstract

Autoimmune thyroiditis (AIT) has a complex etiology and the susceptibility to it is determined by a combination of genetic and environmental factors, although these are not yet fully understood. The present research aimed to explore the DNA methylation patterns in whole blood of extrinsic apoptotic signaling pathway related genes in AIT among areas with different iodine levels. We selected the iodine-fortification areas (IFA), iodine-adequate areas (IAA) and water-based iodine-excess areas (IEA) from Shandong Province of China as survey sites. Totally 176 AIT cases and 176 controls were included. MethylTargetTM and QT-PCR technology were used to detect candidate genes' DNA methylation levels and mRNA expression levels, respectively. We found that DAPK1 DNA methylation levels in AIT cases (especially in female) were significantly higher than controls (t=2.7715, P=0.0059; t=2.4638, P=0.0143 in female). There were differences in DAPK1(t=2.5384, P=0.0121), TNFSF8(t=2.1667, P=0.0334) and TNFAIP8(t=2.5672, P=0.0121) genes methylation between cases and controls with different water iodine levels. The mRNA expression of DAPK1(t=4.329, P<0.001) and TNFAIP8(t=3.775, P<0.001) in the cases were increased. We identified the differences in the DNA methylation status of the extrinsic apoptotic signaling pathway related genes between AIT and controls and in different iodine levels areas. The results were verified at the mRNA level. The environmental iodine may affect DNA methylation to some extent.