自身免疫性甲状腺炎中 KLRC1 和 KLRC3 的 DNA 甲基化：不同水碘暴露的视角。
DNA Methylation of KLRC1 and KLRC3 in Autoimmune Thyroiditis: Perspective of Different Water Iodine Exposure.
机构信息
Disorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang, China;National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin 150081, Heilongjiang, China;Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, Heilongjiang, China.
Division of Health Risk Factor Monitoring and Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China.
出版信息
Biomed Environ Sci. 2024 Sep 20;37(9):1044-1055. doi: 10.3967/bes2024.103.
OBJECTIVE
This study aimed to identify differentially methylated genes (DMGs) associated with natural killer cells in patients with autoimmune thyroiditis (AIT), focusing on the influence of varying water iodine exposure levels.
METHODS
Participants were divided into categories based on median water iodine (MWI) concentrations: iodine-fortified areas (IFA, MWI < 10 µg/L), iodine-adequate areas (IAA, 40 ≤ MWI ≤ 100 µg/L), and iodine-excessive areas (IEA, MWI > 300 µg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89, 40, and 47 pairs for IFA, IAA, and IEA, respectively. DMGs were identified using 850K BeadChip analysis for 10/10 paired samples. Validation of DNA methylation and mRNA expression levels of the DMGs was conducted using MethylTarget™ and QRT-PCR for 176/176 paired samples.
RESULTS
, , and were identified as significant DMGs. Validation revealed that was hypomethylated and highly expressed, whereas was hypermethylated and highly expressed in individuals with AIT. Furthermore, was hypomethylated and highly expressed in both IFA and IEA.
CONCLUSION
The DNA methylation status of and may play crucial roles in AIT pathogenesis. Additionally, DNA methylation of seems to be influenced by different iodine concentrations in water.
目的
本研究旨在鉴定与自身免疫性甲状腺炎（AIT）患者自然杀伤细胞相关的差异甲基化基因（DMGs），重点关注不同水碘暴露水平的影响。
方法
根据中位水碘（MWI）浓度将参与者分为以下几类：碘强化区（IFA，MWI < 10 µg/L）、碘适量区（IAA，40 ≤ MWI ≤ 100 µg/L）和碘过量区（IEA，MWI > 300 µg/L）。共招募了 176 对匹配的 AIT 病例和对照者，并将其分为 IFA、IAA 和 IEA 三组，每组分别有 89、40 和 47 对。使用 850K BeadChip 分析对 10/10 对配对样本进行 DMGs 鉴定。使用 MethylTargetTM 和 QRT-PCR 对 176/176 对配对样本进行 DMGs 的 DNA 甲基化和 mRNA 表达水平验证。
结果
发现 、 、 和 是显著的 DMGs。验证显示，AIT 患者中 呈低甲基化和高表达，而 呈高甲基化和高表达。此外，IFA 和 IEA 中 呈低甲基化和高表达。
结论
和 的 DNA 甲基化状态可能在 AIT 的发病机制中起关键作用。此外，似乎受到水碘浓度不同的影响。
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