INTRODUCTION DNA methylation is an epigenetic mechanism that regulates gene expression and represents an important link between genotype, environment, and disease. It is a reversible and inheritable mechanism that could offer treatment targets. We aimed to assess the methylation changes on specific genes previously associated with Crohn's disease (CD) and to study their possible associations with the pathology. METHODS We included 103 participants and grouped them into 2 cohorts (a first [n = 31] and a second validation [n = 72] cohort), with active CD (aCD) and inactive CD (iCD) and healthy participants (CTR). DNA was obtained from the peripheral blood and analyzed by the Agena platform. The selected genes were catalase (CAT), α-defensin 5 (DEFA5), FasR, FasL, tumor necrosis factor (TNF), TNFRSF1A, TNFRSF1B, PPA2, ABCB1, NOD2, PPARγ, and PKCζ. We used the elastic net algorithm and R software. RESULTS We studied 240 CpGs. Sixteen CpGs showed differential methylation profiles among aCD, iCD, and CTR. We selected for validation those with the greatest differences: DEFA5 CpG_11; CpG_13; CAT CpG_31.32; TNF CpG_4, CpG_12; and ABCB1 CpG_21. Our results validated the genes DEFA5 (methylation gain) and TNF (methylation loss) with P values < 0.001. In both cases, the methylation level was maintained and did not change with CD activity (aCD vs iCD). The subanalysis comparison between aCD and iCD showed significant differential methylation profiles in other CpGs: TNF, FAS, ABCB1, CAT, and TNFRS1BF genes. DISCUSSION The methylation status of DEFA5 and TNF genes provides a signature biomarker that characterizes patients with CD and supports the possible implication of the environment and the immune system in CD pathogenesis.

中文翻译：

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表观遗传甲基化特征的鉴定在克罗恩病中具有临床价值。


引言 DNA 甲基化是一种调节基因表达的表观遗传机制，代表着基因型、环境和疾病之间的重要联系。这是一种可逆且可遗传的机制，可以提供治疗目标。我们的目的是评估先前与克罗恩病 (CD) 相关的特定基因的甲基化变化，并研究它们与病理学的可能关联。方法 我们纳入了 103 名参与者，并将他们分为 2 个队列（第一个 [n = 31] 和第二个验证 [n = 72] 队列），其中包括活动性 CD (aCD) 和非活动性 CD (iCD) 以及健康参与者 (CTR)。从外周血中获取 DNA 并通过 Agena 平台进行分析。所选基因为过氧化氢酶 (CAT)、α-防御素 5 (DEFA5)、FasR、FasL、肿瘤坏死因子 (TNF)、TNFRSF1A、TNFRSF1B、PPA2、ABCB1、NOD2、PPARγ 和 PKCδ。我们使用了弹性网络算法和R软件。结果 我们研究了 240 个 CpG。 16 个 CpG 在 aCD、iCD 和 CTR 之间显示出不同的甲基化谱。我们选择差异最大的进行验证：DEFA5 CpG_11； CpG_13； CAT CpG_31.32； TNF CpG_4、CpG_12；和 ABCB1 CpG_21。我们的结果验证了基因 DEFA5（甲基化增益）和 TNF（甲基化丢失），P 值 < 0.001。在这两种情况下，甲基化水平均保持不变，并且不随 CD 活性而变化（aCD 与 iCD）。 aCD 和 iCD 之间的亚分析比较显示其他 CpG 基因中存在显着差异的甲基化特征：TNF、FAS、ABCB1、CAT 和 TNFRS1BF 基因。讨论 DEFA5 和 TNF 基因的甲基化状态提供了表征 CD 患者特征的标志性生物标志物，并支持环境和免疫系统在 CD 发病机制中的可能影响。