Vats Sakshi, Sundquist Kristina, Wang Xiao, Zarrouk Moncef, Ågren-Witteschus Sophia, Sundquist Jan, Gottsäter Anders, Memon Ashfaque A
Center for Primary Health Care Research, Lund University, Sweden.
Center for Primary Health Care Research, Lund University, Sweden.
Int J Cardiol. 2020 Dec 15;321:137-142. doi: 10.1016/j.ijcard.2020.06.022. Epub 2020 Jun 25.
Abdominal aortic aneurysm (AAA) is a life-threatening condition with a mortality rate of over 80%. Persistent smoking, which is a risk factor for AAA, has lasting effects on DNA methylation. Moreover, a plasma-amino acid, homocysteine, previously implicated in vascular diseases, including aneurysms, has well-established biological association with methylation. In the present study, we aimed to determine the global DNA methylation, homocysteine levels and their association with AAA and its growth. Enzyme-linked immunosorbent assay (ELISA) was used to quantify global DNA methylation in whole blood-DNA samples and diagnostic enzymatic assay quantified plasma homocysteine, from 65-year old men with (n = 116) and without AAA (n = 230) diagnosed at ultrasound screening. We found significantly higher global DNA methylation (p < .001) and homocysteine levels (p < .001) in men with AAA compared to those without AAA, and direct linear associations with baseline aortic diameter. On multivariable regression analysis, global DNA methylation (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.1-2.9) and homocysteine levels (OR: 1.1; 95% CI:1.0-1.1) were positively associated with AAA, independent of smoking, medication use, and major co-morbidities. However, we did not find any significant association between DNA methylation or homocysteine levels with AAA growth during follow-up. We found that global DNA methylation and homocysteine levels are higher in men with AAA but are not associated with AAA growth. This indicates that different pathways and mechanisms may be involved in initiation and progression of AAA. More studies are needed to understand the precise role of DNA methylation, homocysteine and their interplay in AAA pathophysiology.
腹主动脉瘤（AAA）是一种危及生命的疾病，死亡率超过80%。持续吸烟是AAA的一个危险因素，对DNA甲基化有持久影响。此外，一种血浆氨基酸——同型半胱氨酸，此前已被证明与包括动脉瘤在内的血管疾病有关，它与甲基化有着明确的生物学关联。在本研究中，我们旨在确定整体DNA甲基化、同型半胱氨酸水平及其与AAA及其生长的关联。采用酶联免疫吸附测定（ELISA）对全血DNA样本中的整体DNA甲基化进行定量，并使用诊断酶法对血浆同型半胱氨酸进行定量，这些样本来自于在超声筛查中被诊断为患有AAA（n = 116）和未患AAA（n = 230）的65岁男性。我们发现，与未患AAA的男性相比，患AAA的男性的整体DNA甲基化水平（p <.001）和同型半胱氨酸水平（p <.001）显著更高，且与基线主动脉直径呈直接线性关联。在多变量回归分析中，整体DNA甲基化（优势比[OR]：1.8；95%置信区间[CI]：1.1 - 2.9）和同型半胱氨酸水平（OR：1.1；95% CI：1.0 - 1.1）与AAA呈正相关，独立于吸烟、药物使用和主要合并症。然而，在随访期间，我们未发现DNA甲基化或同型半胱氨酸水平与AAA生长之间存在任何显著关联。我们发现，患AAA的男性的整体DNA甲基化和同型半胱氨酸水平较高，但与AAA生长无关。这表明AAA的发生和发展可能涉及不同的途径和机制。需要更多的研究来了解DNA甲基化、同型半胱氨酸及其相互作用在AAA病理生理学中的精确作用。
