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

Yao Chen, Jin Jin Liu, Meng Ying Qu, Bing Xuan Ren, Huai Yong Wu, Li Zhang, Zheng Zhou, Li Xiang Liu, Hong Mei Shen
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摘要

研究目的本研究旨在识别自身免疫性甲状腺炎(AIT)患者体内与自然杀伤细胞相关的差异甲基化基因(DMGs),重点研究不同水碘暴露水平的影响:根据水中碘(MWI)浓度的中位数将参与者分为三类:碘强化地区(IFA,MWI < 10 µg/L)、碘充足地区(IAA,40 ≤ MWI ≤ 100 µg/L)和碘过剩地区(IEA,MWI > 300 µg/L)。共招募了 176 个匹配的 AIT 病例和对照组,并将 IFA、IAA 和 IEA 分别分为 89、40 和 47 对。利用 850K BeadChip 分析法对 10/10 个配对样本进行了 DMGs 鉴定。使用 MethylTarget™ 和 QRT-PCR 对 176/176 个配对样本的 DMGs 的 DNA 甲基化和 mRNA 表达水平进行了验证:结果:KLRC1、KLRC3和SH2D1B被鉴定为重要的DMGs。验证结果显示,在 AIT 患者中,KLRC1 低甲基化且高表达,而 KLRC3 高甲基化且高表达。此外,KLRC1在IFA和IEA中均呈低甲基化和高表达:结论:KLRC1 和 KLRC3 的 DNA 甲基化状态可能在 AIT 发病机制中起着关键作用。结论:KLRC1和KLRC3的DNA甲基化状态可能在AIT发病机制中起关键作用。此外,KLRC1的DNA甲基化似乎受水中不同碘浓度的影响。
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DNA Methylation of KLRC1 and KLRC3 in Autoimmune Thyroiditis: Perspective of Different Water Iodine Exposure.

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: KLRC1, KLRC3, and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed, whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore, KLRC1 was hypomethylated and highly expressed in both IFA and IEA.

Conclusion: The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally, DNA methylation of KLRC1seems to be influenced by different iodine concentrations in water.

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