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惊恐障碍女性患者中FOXP3启动子的高甲基化与免疫系统早衰?

Hypermethylation of FOXP3 Promoter and Premature Aging of the Immune System in Female Patients with Panic Disorder?

作者信息

Prelog Martina, Hilligardt Deborah, Schmidt Christian A, Przybylski Grzegorz K, Leierer Johannes, Almanzar Giovanni, El Hajj Nady, Lesch Klaus-Peter, Arolt Volker, Zwanzger Peter, Haaf Thomas, Domschke Katharina

机构信息

Department of Pediatrics, University Hospital Wuerzburg, Wuerzburg, Germany.

Clinic for Internal Medicine C, University of Greifswald, Greifswald, Germany.

出版信息

PLoS One. 2016 Jun 30;11(6):e0157930. doi: 10.1371/journal.pone.0157930. eCollection 2016.

DOI:10.1371/journal.pone.0157930
PMID:27362416
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4928917/
Abstract

Immunological abnormalities associated with pathological conditions, such as higher infection rates, inflammatory diseases, cancer or cardiovascular events are common in patients with panic disorder. In the present study, T cell receptor excision circles (TRECs), Forkhead-Box-Protein P3 gene (FOXP3) methylation of regulatory T cells (Tregs) and relative telomere lengths (RTLs) were investigated in a total and subsamples of 131 patients with panic disorder as compared to 131 age- and sex-matched healthy controls in order to test for a potential dysfunction and premature aging of the immune system in anxiety disorders. Significantly lower TRECs (p = 0.004) as well as significant hypermethylation of the FOXP3 promoter region (p = 0.005) were observed in female (but not in male) patients with panic disorder as compared to healthy controls. No difference in relative telomere length was discerned between patients and controls, but significantly shorter telomeres in females, smokers and older persons within the patient group. The presently observed reduced TRECs in panic disorder patients and FOXP3 hypermethylation in female patients with panic disorder potentially reflect impaired thymus and immunosuppressive Treg function, which might partly account for the known increased morbidity and mortality of anxiety disorders conferred by e.g. cancer and cardiovascular disorders.

摘要

与病理状况相关的免疫异常,如感染率升高、炎症性疾病、癌症或心血管事件,在惊恐障碍患者中很常见。在本研究中,对131例惊恐障碍患者及其亚组样本,与131例年龄和性别匹配的健康对照进行了T细胞受体切除环(TRECs)、调节性T细胞(Tregs)的叉头框蛋白P3基因(FOXP3)甲基化以及相对端粒长度(RTLs)的研究,以检测焦虑症患者免疫系统是否存在潜在功能障碍和早衰。与健康对照相比,在女性(而非男性)惊恐障碍患者中观察到显著更低的TRECs(p = 0.004)以及FOXP3启动子区域的显著高甲基化(p = 0.005)。患者与对照之间相对端粒长度无差异,但在患者组中,女性、吸烟者和老年人的端粒显著更短。目前在惊恐障碍患者中观察到的TRECs减少以及女性惊恐障碍患者中的FOXP3高甲基化,可能反映了胸腺功能受损和免疫抑制性Treg功能异常,这可能部分解释了焦虑症已知的由癌症和心血管疾病等导致的发病率和死亡率增加的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fe2/4928917/2ca120c7536d/pone.0157930.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fe2/4928917/d19811821163/pone.0157930.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fe2/4928917/5cfebad44569/pone.0157930.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fe2/4928917/2ca120c7536d/pone.0157930.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fe2/4928917/d19811821163/pone.0157930.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fe2/4928917/5cfebad44569/pone.0157930.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fe2/4928917/2ca120c7536d/pone.0157930.g003.jpg

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