Borderline personality disorder (BPD) is a severe and highly prevalent psychiatric disorder, more common in females than in males and with notable differences in presentation between genders. Recent studies have shown that epigenetic modifications such as DNA methylation may modulate gene × environment interactions and impact on neurodevelopment. We conducted an epigenome wide study (Illumina Infinium HumanMethylation450k beadchip) in a group of BPD patients with (N = 49) and without (N = 47) childhood traumas and in a control group (N = 44). Results were confirmed in a replication cohort (N = 293 BPD patients and N = 114 controls) using EpiTYPER assays. Differentially methylated CpG sites were observed in several genes and intragenic regions in the X chromosome (PQBP1, ZNF41, RPL10, cg07810091 and cg24395855) and in chromosome 6 (TAP2). BPD patients showed significantly lower methylation levels in these CpG sites than healthy controls. These differences seemed to be increased by the existence of childhood trauma. Comparisons between BPD patients with childhood trauma and patients and controls without revealed significant differences in four genes (POU5F1, GGT6, TNFRSF13C and FAM113B), none of them in the X chromosome. Gene set enrichment analyses revealed that epigenetic alterations were more frequently found in genes controlling oestrogen regulation, neurogenesis and cell differentiation. These results suggest that epigenetic alterations in the X chromosome and oestrogen-regulation genes may contribute to the development of BPD and explain the differences in presentation between genders. Furthermore, childhood trauma events may modulate the magnitude of the epigenetic alterations contributing to BPD.

交际型人格障碍（BPD）是一种严重且高度流行的精神病，在女性中比男性更常见，并且在性别表现上存在显着差异。最近的研究表明，表观遗传学修饰（例如DNA甲基化）可能会调节基因与环境的相互作用并影响神经发育。我们对一组患有（N  = 49），没有（N  = 47）儿童期创伤的BPD患者和一组对照组（N  = 44）进行了表观基因组范围的研究（Illumina Infinium HumanMethylation450k beadchip ）。复制队列（N  = 293 BPD患者和N = 114个对照）使用EpiTYPER分析。在X染色体（PQBP1，ZNF41，RPL10，cg07810091和cg24395855）和6号染色体（TAP2）的几个基因和基因内区域中观察到差异甲基化的CpG位点。BPD患者在这些CpG位点的甲基化水平明显低于健康对照。儿童期创伤的存在似乎加剧了这些差异。患有儿童创伤的BPD患者与未患病的BPD患者和对照组之间的比较显示四个基因（POU5F1，GGT6，TNFRSF13C和FAM113B）存在显着差异），它们都不在X染色体上。基因集富集分析显示，在控制雌激素调节，神经发生和细胞分化的基因中，表观遗传改变更为常见。这些结果表明，X染色体上的表观遗传学改变和雌激素调节基因可能有助于BPD的发展，并解释了性别在表现上的差异。此外，儿童期创伤事件可能会调节导致BPD的表观遗传改变的程度。