Qu Mengying, Wan Siyuan, Wu Huaiyong, Ren Bingxuan, Chen Yao, Liu Lixiang, Shen Hongmei
Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang150081, People's Republic of China.
Division of Health Risk Factor Monitoring and Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai200336, People's Republic of China.
Br J Nutr. 2023 Jan 28;129(2):206-217. doi: 10.1017/S0007114522000721. Epub 2022 Mar 9.
Autoimmune thyroiditis (AIT) has a complex aetiology 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 signalling pathway-related genes in AIT among areas with different iodine levels. We selected the iodine-fortification areas, iodine-adequate areas and water-based iodine-excess areas from Shandong Province of China as survey sites. Totally, 176 AIT cases and 176 controls were included. MethylTarget and QT-PCR technology were used to detect candidate genes' DNA methylation levels and mRNA expression levels, respectively. We found that death associated protein kinase 1 (DAPK1) DNA methylation levels in AIT cases (especially in female) were significantly higher than controls ( = 2·7715, = 0·0059; = 2·4638, = 0·0143 in female). There were differences in DAPK1 ( = 2·5384, = 0·0121), TNF superfamily member 8 ( = 2·1667, = 0·0334) and TNF--induced protein 8 (TNFAIP8) ( = 2·5672, = 0·0121) genes methylation between cases and controls with different water iodine levels. The mRNA expression of DAPK1 ( = 4·329, < 0·001) and TNFAIP8 ( = 3·775, < 0·001) in the cases was increased. We identified the differences in the DNA methylation status of the extrinsic apoptotic signalling 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.
自身免疫性甲状腺炎(AIT)病因复杂,其易感性由遗传和环境因素共同决定,尽管目前尚未完全明确这些因素。本研究旨在探讨不同碘水平地区AIT患者外周血中与外源性凋亡信号通路相关基因的DNA甲基化模式。我们选取中国山东省的碘强化地区、碘充足地区和水源性碘过量地区作为调查地点。共纳入176例AIT患者和176例对照。分别采用MethylTarget和QT-PCR技术检测候选基因的DNA甲基化水平和mRNA表达水平。我们发现,AIT患者(尤其是女性)中死亡相关蛋白激酶1(DAPK1)的DNA甲基化水平显著高于对照组(女性:t = 2·7715,P = 0·0059;t = 2·4638,P = 0·0143)。不同水碘水平的病例与对照之间,DAPK1(t = 2·5384,P = 0·0121)、肿瘤坏死因子超家族成员8(t = 2·1667,P = 0·0334)和肿瘤坏死因子诱导蛋白8(TNFAIP8)(t = 2·5672,P = 0·0121)基因的甲基化存在差异。病例组中DAPK1(t = 4·329,P < 0·001)和TNFAIP8(t = 3·775,P < 0·001)的mRNA表达增加。我们确定了AIT与对照之间以及不同碘水平地区外源性凋亡信号通路相关基因的DNA甲基化状态差异。结果在mRNA水平得到验证。环境碘可能在一定程度上影响DNA甲基化。