Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels.

IF 2.5 Q3 GENETICS & HEREDITY
Andrea Stoccoro, Martina Lari, Lucia Migliore, Fabio Coppedè
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Abstract

Background/objectives: One-carbon metabolism is a critical pathway for epigenetic mechanisms. Circulating biomarkers of one-carbon metabolism have been associated with changes in nuclear DNA methylation levels in individuals affected by age-related diseases. More and more studies are showing that even mitochondrial DNA (mtDNA) could be methylated. In particular, methylation of the mitochondrial displacement (D-loop) region modulates the gene expression and replication of mtDNA and, when altered, can contribute to the development of human illnesses. However, no study until now has demonstrated an association between circulating biomarkers of one-carbon metabolism and D-loop methylation levels.

Methods: In the study presented herein, we searched for associations between circulating one-carbon metabolism biomarkers, including folate, homocysteine, and vitamin B12, and the methylation levels of the D-loop region in DNA obtained from the peripheral blood of 94 elderly voluntary subjects.

Results: We observed a positive correlation between D-loop methylation and vitamin B12 (r = 0.21; p = 0.03), while no significant correlation was observed with folate (r = 0.02; p = 0.80) or homocysteine levels (r = 0.02; p = 0.82). Moreover, D-loop methylation was increased in individuals with high vitamin B12 levels compared to those with normal vitamin B12 levels (p = 0.04).

Conclusions: This is the first study suggesting an association between vitamin B12 circulating levels and mtDNA methylation in human subjects. Given the potential implications of altered one-carbon metabolism and mitochondrial epigenetics in human diseases, a deeper understanding of their interaction could inspire novel interventions with beneficial effects for human health.

一碳代谢循环生物标志物与线粒体 D 环区甲基化水平之间的关系
背景/目的:一碳代谢是表观遗传机制的关键途径。一碳代谢的循环生物标志物与受老年相关疾病影响的个体核 DNA 甲基化水平的变化有关。越来越多的研究表明,甚至线粒体 DNA(mtDNA)也可能被甲基化。尤其是线粒体位移(D-环)区域的甲基化会调节 mtDNA 的基因表达和复制,一旦发生改变,就会导致人类疾病的发生。然而,迄今为止还没有研究证明一碳代谢的循环生物标志物与 D 环甲基化水平之间存在关联:在本文介绍的研究中,我们寻找了循环一碳代谢生物标志物(包括叶酸、同型半胱氨酸和维生素 B12)与 94 名老年自愿受试者外周血 DNA 中 D 环区域甲基化水平之间的关联:我们观察到 D 环甲基化与维生素 B12 呈正相关(r = 0.21;p = 0.03),而与叶酸(r = 0.02;p = 0.80)或同型半胱氨酸水平(r = 0.02;p = 0.82)无明显相关性。此外,与维生素 B12 水平正常的人相比,维生素 B12 水平高的人 D 环甲基化增加(p = 0.04):这是第一项表明人体维生素 B12 循环水平与 mtDNA 甲基化之间存在关联的研究。鉴于一碳代谢和线粒体表观遗传学的改变对人类疾病的潜在影响,深入了解它们之间的相互作用可激发新的干预措施,从而对人类健康产生有益影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Epigenomes
Epigenomes GENETICS & HEREDITY-
CiteScore
3.80
自引率
0.00%
发文量
38
审稿时长
11 weeks
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