Non-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines. We confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual’s methylation status is associated with the mother’s age and socioeconomic status, but not with the individual’s own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood. These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.

中文翻译：

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nc886 表观等位基因的甲基化状态反映了围孕期状况，并通过 nc886 RNA 与葡萄糖代谢相关

非编码 RNA 886 (nc886) 由母系遗传的亚稳态表观等位基因编码。我们着手研究 nc886 表观等位基因甲基化模式的决定因素和动态，以及这种甲基化状态如何与 nc886 RNA 表达相关。此外，我们研究了 YFS 和 KORA 队列中 nc886 甲基化状态或 nc886 RNA 水平与代谢特征之间的关联。nc886 表观等位基因甲基化与 RNA 表达之间的关联也在诱导多能干细胞 (iPSC) 系中得到了验证。我们确认 nc886 表观等位基因的甲基化状态大多是二项式的，个体表现出非甲基化或半甲基化状态，但我们也描述了中间和接近完全甲基化的个体。我们表明，个体的甲基化状态与母亲的年龄和社会经济地位有关，但与个体自身的遗传无关。一旦建立，NC886 表观等位基因的甲基化状态将保持稳定至少 25 年。这种甲基化状态与血清、血液和 iPSC 系中 nc886 非编码 RNA 的水平密切相关。此外，nc886甲基化状态与青春期的葡萄糖和胰岛素水平相关，但与成年后的糖代谢指标或2型糖尿病的发病率无关。然而，nc886-3p RNA 水平也与成年期的葡萄糖代谢相关。这些结果表明 nc886 亚稳态表观等位基因甲基化是通过围孕条件调节的，并且它通过表观等位基因区域编码的 ncRNA 的表达与葡萄糖代谢相关。