DNA 甲基化与 BMI 之间的关联因代谢健康状况而异：这可能与不同的心血管结局有关。
Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes.
机构信息
Nutrition and Health Sciences Program, Laney Graduate School, Emory University, 1518 Clifton Rd, Atlanta, GA, 30322, USA.
Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, CA, USA.
出版信息
Clin Epigenetics. 2021 Dec 22;13(1):230. doi: 10.1186/s13148-021-01194-3.
BACKGROUND
Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health.
RESULTS
The discovery study population was derived from three Women's Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation β values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm β value, the risk of incident CHD increased by 9% in one site and decreased by 6-10% in two sites over 25 years.
CONCLUSIONS
Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health.
背景
体重指数（BMI）是心血管不良结局的一个众所周知的危险因素，与差异 DNA 甲基化（DNAm）有关。同样，代谢健康也与 DNAm 的变化有关。目前尚不清楚 BMI 以外的整体代谢健康状况如何改变 BMI 与甲基化谱之间的关系，以及这可能对下游心血管疾病产生什么影响。本研究的目的是确定在整体代谢健康状况下，BMI 与 DNAm 之间关联可能受到修饰的胞嘧啶-磷酸-鸟嘌呤（CpG）位点。
结果
发现研究人群来自三个妇女健康倡议（WHI）辅助研究（n=3977）和两个社区动脉粥样硬化风险研究（ARIC）辅助研究（n=3520）。研究结果在多民族动脉粥样硬化研究（MESA）队列中得到了验证（n=1200）。广义线性模型将甲基化β值回归到 BMI 和代谢健康 Z 分数（BMI×MHZ）的交互作用上，该模型调整了 BMI、MHZ、细胞成分、芯片数量和位置、研究特征、前三个祖先主成分、吸烟、年龄、种族（WHI）和性别（ARIC）。在检查的 429566 个位点中，BMI×MHZ 与 DNAm 之间的差异关联在 22 个 CpG 位点被确定（FDR q<0.05），其中一个位点在 MESA 中得到了复制（cg18989722，位于 TRAPPC9 基因中）。22 个位点中有 3 个与 WHI 中的冠心病（CHD）发病有关。在一个位点中，DNAm β 值每增加 0.01 个单位，CHD 发病风险增加 9%，在另外两个位点中，CHD 发病风险分别降低 6-10%，随访时间为 25 年。
结论
在 MHZ 下，DNAm 与 BMI 之间的差异关联在 22 个位点被确定，其中一个位点得到了验证（cg18989722），三个位点与 CHD 发病有关。这些位点位于几个与 NF-kappa-B 信号传导有关的基因中，这表明在 DNA 甲基化和 BMI 相关代谢健康之间，炎症可能起作用。
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