译 者:刘振华(河北保定252医院)
译者简介:刘振华,硕士研究生,河北保定解放军82集团军医院(原解放军252医院)中医康复科主治医师,现任中国中医药研究促进会青年医师分会委员,保定市风湿病学专业委员会委员。2019年于北医三院学习,师从刘湘源教授,系统学习免疫性不良受孕的诊断及治疗。
择要
目的:本研究的紧张目的是确定类风湿性枢纽关头炎(RA)母亲所生孩子的DNA甲基化谱是否与一样平常人群母亲所生孩子的甲基化谱不同。此外,我们的目的是确定甲基化的差异是否与孕期RA疾病活动或药物利用干系。
方法:在这项研究中,在胞嘧啶磷酸鸟嘌呤位点丈量全基因组DNA甲基化,利用来自患有RA母亲所生儿童(均匀年事即是6.8岁)的80份血液样本中得到的甲基化450k芯片。利用来自基于群体R代研究的354名儿童(均匀年事即是6.0岁)的血液样品作为对照。进行线性稠浊模型以研究各组之间的甲基化差异,校正干系的殽杂成分。
结果:RA母亲所生孩子的血液样本与与对照血液样本之间共有147个胞嘧啶磷酸鸟嘌呤位点甲基化差异,5种最显著干系的胞嘧啶磷酸鸟嘌呤位点是cg06642177,cg08867893,cg06778273, cg07786668和cg20116574。甲基化的差异与受孕期母体RA疾病活动或药物利用无关。
结论:147个胞嘧啶磷酸鸟嘌呤位点的DNA甲基化在RA母亲所生孩子和一样平常人群母亲所生孩子之间存在差异。目前尚不清楚所确定的关联是否是因果关系,如果是,它们是否由疾病或治疗引起。有必要进行更多的研究,包括复制这些结果,以进一步研究该结果与患有类风湿性枢纽关头炎的母亲所生儿童的远期康健的干系性。
附原文:ABSTRACT:OBJECTIVES:The main objective of this study was to determine whether the DNA methylation profile of children born to mothers with rheumatoid arthritis (RA) is different from that of children born to mothers from the general population. In addition, we aimed to determine whether any differences in methylation are associated with maternal RA disease activity or medication use during pregnancy. METHODS:For this study, genome-wide DNA methylation was measured at cytosine-phosphate-guanine (CpG) sites, using the Infinium Illumina HumanMethylation 450K BeadChip, in 80 blood samples from children (mean age=6.8 years) born to mothers with RA. As controls, blood samples from 354 children (mean age=6.0 years) from the population-based Generation R Study were used. Linear mixed models were performed to investigate differential methylation between the groups, corrected for relevant confounders. RESULTS:A total of 147 CpGs were differentially methylated between blood samples of children born to mothers with RA and the control blood samples. The five most significantly associated CpGs were cg06642177, cg08867893, cg06778273, cg07786668 and cg20116574. The differences in methylation were not associated with maternal RA disease activity or medication use during pregnancy. CONCLUSIONS:DNA methylation at 147 CpGs differed between children born to mothers with RA and children born to mothers from the general population. It remains unknown whether the identified associations are causal, and if so whether they are caused by the disease or treatment. More research, including replication of these results, is necessary in order to strengthen the relevance of our findings for the later-life health of children born to mothers with RA.
引自:Ince-Askan Hilal; Mandaviya Pooja R; Felix Janine F; Duijts Liesbeth; van Meurs Joyce B; Hazes Johanna M W; Dolhain Radboud J E M.Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy.Annals of the rheumatic diseases.2019;DOI: 10.1136/annrheumdis-2018-214930