Differential DNA methylation in peripheral tissues has been associated with Borderline Personality Disorder (BPD). Alterations have been found in several genes, among them the Catechol-O-methyltransferase (COMT) gene. COMT is a known neuropsychiatric candidate gene, which contains a genotype variant (Val108/158Met) that affects protein function and has been found associated with several psychiatric disorders. In addition, this variant also affects COMT DNA methylation. However, in previous epigenetic studies, the DNA methylation results have not always been controlled for genotype, even though overrepresentation of the Met allele has been frequently reported in cohorts of BPD patients. Therefore, in the present study, we investigated whether alteration of COMT DNA methylation in BPD patients is indeed associated with mental health status or merely influenced by a differential distribution of the COMT genotype between BPD patients and healthy control individuals. We found significant group differences, as well as a strong effect of genotype on COMT DNA methylation. While the direction of effect was different compared to a previous study, our study supports the finding of altered COMT DNA methylation in patients with BPD and reinforces the need to include genotype information in future DNA methylation studies of COMT.

中文翻译：

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边缘型人格障碍患者的差异 COMT DNA 甲基化：基因型很重要

外周组织中的差异 DNA 甲基化与边缘型人格障碍 (BPD) 相关。已经在几个基因中发现了改变，其中包括儿茶酚-O-甲基转移酶 (COMT) 基因。COMT 是一种已知的神经精神病学候选基因，它包含影响蛋白质功能的基因型变异 (Val108/158Met)，已发现与多种精神疾病有关。此外，该变体还影响 COMT DNA 甲基化。然而，在之前的表观遗传研究中，DNA 甲基化结果并不总是针对基因型进行控制，即使在 BPD 患者队列中经常报道 Met 等位基因的过度表达。因此，在本研究中，我们调查了 BPD 患者 COMT DNA 甲基化的改变是否确实与心理健康状况有关，或者仅受 BPD 患者和健康对照个体之间 COMT 基因型差异分布的影响。我们发现显着的组间差异，以及基因型对 COMT DNA 甲基化的强烈影响。虽然与之前的研究相比，效果的方向不同，但我们的研究支持 BPD 患者 COMT DNA 甲基化改变的发现，并加强了在未来 COMT 的 DNA 甲基化研究中包括基因型信息的必要性。