Abstract：
BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease characterized by recurring fever, erythema, joint pain, and abdominal discomfort during acute episodes. While FMF patients typically share MEFV gene mutations, they display varying clinical manifestations, suggesting the involvement of modifying genes, epigenetic mechanisms, or environmental factors. G protein regulator signal 10 (RGS10), a member of the RGS protein family, exhibits anti-inflammatory effects in autoinflammatory diseases. There are no studies on the role of plays in FMF pathogenesis or histone modification in FMF.
OBJECTIVE: This study aimed to shed light on the epigenetic regulation of FMF from several perspectives. The relationship between RGS10 DNA hypermethylation in FMF clinical parameters and the regulation of 22 histone modifications were examined in FMF attack patients and the control group.
METHODS: Sixty FMF (remission/attack) and thirty healthy individuals were included in the study. First, RNA was isolated from the blood of patients/controls, and the expression of RGS10 was examined. Then, DNA was isolated from the patients, and gene-specific hypermethylation was investigated using the bisulfite conversion method. Finally, histone extraction was performed for FMF patients and controls and 22 histone H3 modifications were determined. In addition, using ADEX bioinformatics tools, RGS10 expression and methylation profiles were detected in different autoinflammatory diseases.
RESULTS: This study indicate that RGS10 expression decreased in attack-free/attack patients than control, attributed to DNA methylation. In addition, there were a positive correlation between FMF patients and attack, WBC, neutrophil, MCHC and MPV. Moreover, higher H3K4 me3, H3K9 me2, and H3K14ac levels were observed in patients with FMF attacks. This research also showed a consistent decrease in RGS10 expression in patients with SjS, SSc, and T1D compared with controls. I also obtained five prognosis-related CpGs (cg17527393, cg19653161, cg20445950, cg18938673 and cg13975098) of RGS10 in patients with SjS, RA, SSc, SLE and T1D.
CONCLUSIONS: The present study provides insights into the complex relationship between RGS10, epigenetic modifications, and immune responses in FMF. While RGS10 may initially enhance immune responses, genetic mutations and epigenetic changes associated with FMF acute episode may override this regulatory effect, resulting in increased inflammation and clinical symptoms. Moreover, our study revealed elevated levels of specific histone modifications in the context of FMF, suggesting significant epigenetic changes that could contribute to the disease pathogenesis. Understanding these associations opens new avenues for research and potential therapeutic interventions, potentially involving epigenetic therapies targeting histone modifications.
OBJECTIVE: This study aimed to shed light on the epigenetic regulation of FMF from several perspectives. The relationship between RGS10 DNA hypermethylation in FMF clinical parameters and the regulation of 22 histone modifications were examined in FMF attack patients and the control group.
METHODS: Sixty FMF (remission/attack) and thirty healthy individuals were included in the study. First, RNA was isolated from the blood of patients/controls, and the expression of RGS10 was examined. Then, DNA was isolated from the patients, and gene-specific hypermethylation was investigated using the bisulfite conversion method. Finally, histone extraction was performed for FMF patients and controls and 22 histone H3 modifications were determined. In addition, using ADEX bioinformatics tools, RGS10 expression and methylation profiles were detected in different autoinflammatory diseases.
RESULTS: This study indicate that RGS10 expression decreased in attack-free/attack patients than control, attributed to DNA methylation. In addition, there were a positive correlation between FMF patients and attack, WBC, neutrophil, MCHC and MPV. Moreover, higher H3K4 me3, H3K9 me2, and H3K14ac levels were observed in patients with FMF attacks. This research also showed a consistent decrease in RGS10 expression in patients with SjS, SSc, and T1D compared with controls. I also obtained five prognosis-related CpGs (cg17527393, cg19653161, cg20445950, cg18938673 and cg13975098) of RGS10 in patients with SjS, RA, SSc, SLE and T1D.
CONCLUSIONS: The present study provides insights into the complex relationship between RGS10, epigenetic modifications, and immune responses in FMF. While RGS10 may initially enhance immune responses, genetic mutations and epigenetic changes associated with FMF acute episode may override this regulatory effect, resulting in increased inflammation and clinical symptoms. Moreover, our study revealed elevated levels of specific histone modifications in the context of FMF, suggesting significant epigenetic changes that could contribute to the disease pathogenesis. Understanding these associations opens new avenues for research and potential therapeutic interventions, potentially involving epigenetic therapies targeting histone modifications.
摘要：
背景：家族性地中海热（FMF）是一种常染色体隐性自身炎性疾病，其特征是反复发热，红斑,关节痛,急性发作时腹部不适。虽然FMF患者通常共享MEFV基因突变，它们表现出不同的临床表现，暗示了修饰基因的参与，表观遗传机制，或环境因素。G蛋白调节信号10（RGS10），RGS蛋白家族的一员,在自身炎性疾病中表现出抗炎作用。尚无关于在FMF发病机理或FMF组蛋白修饰中的作用的研究。
目的：本研究旨在从多个角度阐明FMF的表观遗传调控。在FMF发作患者和对照组中检查了FMF临床参数中RGS10DNA高甲基化与22种组蛋白修饰调节之间的关系。
方法：研究包括60个FMF（缓解/发作）和30个健康个体。首先,从患者/对照组的血液中分离出RNA，检测RGS10的表达。然后，从病人身上分离出DNA,并使用亚硫酸氢盐转换方法研究了基因特异性的超甲基化。最后,对FMF患者和对照组进行组蛋白提取，并确定了22个组蛋白H3修饰。此外,使用ADEX生物信息学工具，在不同的自身炎性疾病中检测到RGS10的表达和甲基化谱。
结果：这项研究表明，无发作/发作患者的RGS10表达比对照组降低，归因于DNA甲基化。此外,FMF患者与发作呈正相关，WBC,中性粒细胞,MCHC和MPV。此外，在FMF发作患者中观察到更高的H3K4me3,H3K9me2和H3K14ac水平.这项研究还表明，在SjS患者中，RGS10表达持续下降，SSc,和T1D与对照组相比。我还获得了SjS患者RGS10的五个预后相关CpG（cg17527393，cg19653161，cg20445950，cg18938673和cg13975098），RA,SSc,SLE和T1D。
结论：本研究提供了对RGS10，表观遗传修饰，和FMF中的免疫反应。虽然RGS10最初可能会增强免疫反应，与FMF急性发作相关的基因突变和表观遗传变化可能会覆盖这种调节作用，导致炎症和临床症状增加。此外，我们的研究表明，在FMF的背景下，特定组蛋白修饰水平升高，提示显著的表观遗传变化可能有助于疾病的发病机制。了解这些关联为研究和潜在的治疗干预开辟了新的途径。潜在涉及针对组蛋白修饰的表观遗传疗法。
目的：本研究旨在从多个角度阐明FMF的表观遗传调控。在FMF发作患者和对照组中检查了FMF临床参数中RGS10DNA高甲基化与22种组蛋白修饰调节之间的关系。
方法：研究包括60个FMF（缓解/发作）和30个健康个体。首先,从患者/对照组的血液中分离出RNA，检测RGS10的表达。然后，从病人身上分离出DNA,并使用亚硫酸氢盐转换方法研究了基因特异性的超甲基化。最后,对FMF患者和对照组进行组蛋白提取，并确定了22个组蛋白H3修饰。此外,使用ADEX生物信息学工具，在不同的自身炎性疾病中检测到RGS10的表达和甲基化谱。
结果：这项研究表明，无发作/发作患者的RGS10表达比对照组降低，归因于DNA甲基化。此外,FMF患者与发作呈正相关，WBC,中性粒细胞,MCHC和MPV。此外，在FMF发作患者中观察到更高的H3K4me3,H3K9me2和H3K14ac水平.这项研究还表明，在SjS患者中，RGS10表达持续下降，SSc,和T1D与对照组相比。我还获得了SjS患者RGS10的五个预后相关CpG（cg17527393，cg19653161，cg20445950，cg18938673和cg13975098），RA,SSc,SLE和T1D。
结论：本研究提供了对RGS10，表观遗传修饰，和FMF中的免疫反应。虽然RGS10最初可能会增强免疫反应，与FMF急性发作相关的基因突变和表观遗传变化可能会覆盖这种调节作用，导致炎症和临床症状增加。此外，我们的研究表明，在FMF的背景下，特定组蛋白修饰水平升高，提示显著的表观遗传变化可能有助于疾病的发病机制。了解这些关联为研究和潜在的治疗干预开辟了新的途径。潜在涉及针对组蛋白修饰的表观遗传疗法。
