血浆磷脂花生四烯酸与心血管疾病的关联：一项孟德尔随机研究。

The associations of plasma phospholipid arachidonic acid with cardiovascular diseases: A Mendelian randomization study.

机构信息

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; School of Public Health and Health Policy, City University of New York, New York, NY, USA.

出版信息

EBioMedicine. 2021 Jan;63:103189. doi: 10.1016/j.ebiom.2020.103189. Epub 2021 Jan 6.

DOI:10.1016/j.ebiom.2020.103189

PMID:33418501

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7804604/

Abstract

BACKGROUND

Arachidonic acid (AA), a major long-chain n-6 polyunsaturated fatty acid in animal foods, has been linked to inflammation, coagulation, and testosterone, which might relate to atherosclerotic cardiovascular diseases (ASCVD). We assessed the associations of genetically predicted plasma phospholipid AA with ASCVD and other CVD overall and by sex using Mendelian randomization (MR).

METHODS

We conducted two-sample MR, applying eight genetic variants, independent of a highly pleiotropic variant (rs174547), strongly (p < 5 × 10) predicting AA, primarily to summary statistics of genetic associations with ASCVD, including ischaemic heart disease (IHD), ischaemic stroke, and peripheral artery disease (PAD) from CARDIoGRAMplusC4D 1000 Genomes (60,801 IHD cases, 123,504 controls), MEGASTROKE (34,217 ischaemic stroke cases, 406,111 controls), and Pan-UK Biobank (n=~420,531), and secondarily to genetic associations with other CVD from Pan-UK Biobank, Atrial Fibrillation Consortium, HERMES consortium, and FinnGen. We also assessed sex differences.

FINDINGS

Genetically predicted AA was associated with ASCVD (odds ratio (OR) per % of total fatty acids increase 1.03, 95% confidence interval (CI) 1.01 to 1.05) and its subtypes IHD (OR 1.03, 95% CI 1.004 to 1.05), ischaemic stroke (OR 1.03, 95% CI 1.004 to 1.06) and possibly PAD (OR 1.08, 95% CI 1.00 to 1.17), possibly more strongly in men than women. AA was also associated with venous thromboembolism (OR 1.12, 95% CI 1.05 to 1.19). A similar pattern was observed when using rs174547 to genetically predict AA.

INTERPRETATION

Our study suggests positive associations of AA with ASCVD and venous thromboembolism, with possibly stronger associations in men than women.

FUNDING

No funding.

摘要

背景

花生四烯酸（AA）是动物食品中主要的长链 n-6 多不饱和脂肪酸，与炎症、凝血和睾酮有关，这可能与动脉粥样硬化性心血管疾病（ASCVD）有关。我们使用孟德尔随机化（MR）评估了遗传预测的血浆磷脂 AA 与 ASCVD 及其他心血管疾病（CVD）的相关性，以及按性别分层的相关性。

方法

我们进行了两样本 MR 分析，应用了 8 个独立于高度多效性变异（rs174547）的遗传变异，这些变异强烈（p < 5×10）预测 AA，主要用于基于遗传关联的汇总统计数据，与 ASCVD 相关，包括缺血性心脏病（IHD）、缺血性中风和外周动脉疾病（PAD），这些数据来自 CARDIoGRAMplusC4D 1000 基因组（60801 例 IHD 病例，123504 例对照）、MEGASTROKE（34217 例缺血性中风病例，406111 例对照）和 Pan-UK Biobank（n=~420531），其次是与 Pan-UK Biobank、心房颤动联盟、HERMES 联盟和 FinnGen 中的其他 CVD 遗传关联。我们还评估了性别差异。

结果

遗传预测的 AA 与 ASCVD 相关（每增加总脂肪酸的百分比，比值比（OR）为 1.03，95%置信区间（CI）为 1.01 至 1.05）及其亚型 IHD（OR 1.03，95%CI 为 1.004 至 1.05）、缺血性中风（OR 1.03，95%CI 为 1.004 至 1.06）和可能的 PAD（OR 1.08，95%CI 为 1.00 至 1.17），可能在男性中比女性更强烈。AA 还与静脉血栓栓塞（OR 1.12，95%CI 为 1.05 至 1.19）相关。当使用 rs174547 来遗传预测 AA 时，也观察到了类似的模式。