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基因预测的原发性醛固酮增多症与主动脉瘤和主动脉夹层之间的因果关联:一项孟德尔随机化研究。

Causal association between genetically predicted primary aldosteronism and aortic aneurysm and aortic dissection: A Mendelian randomization study.

作者信息

Liu Sen, Wan Jindong, Yang Yi, Wang Dan, Hou Jixin, Wang Peijian

机构信息

Department of Cardiology, Department of Clinical Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.

Key Laboratory of Aging and Vascular Homeostasis at Chengdu Medical College of Sichuan Province, Chengdu, Sichuan, China.

出版信息

Medicine (Baltimore). 2025 Mar 21;104(12):e41951. doi: 10.1097/MD.0000000000041951.

Abstract

Emerging research indicates a potential pathogenic overlap between primary aldosteronism (PA) and aortic aneurysm (AA)/aortic dissection (AD). Despite case reports suggest a potential link between PA and AA/AD, the causality of this relationship remains unclear. This study is the first to elucidate the causal association between genetically predicted PA and the risk of AA and AD through Mendelian randomization (MR) analysis. Genome-wide significant single nucleotide polymorphisms associated with PA were identified from publicly available genome-wide association study summary statistics. Genetic associations with AA and AD were obtained from the FinnGen database. The inverse-variance weighted (IVW) method, along with complementary MR analysis methods, was employed to generate primary estimates. Sensitivity analyses were performed to ensure the robustness of findings. MR analyses utilizing the IVW method revealed a significant causal association between genetically predicted PA and the risk of AA (OR = 1.038; 95% CI = 1.024-1.053; P < .01), thoracic AA (OR = 1.066; 95% CI = 1.045-1.087; P < .01) and AD (OR = 1.165; 95% CI = 1.113-1.219; P < .01). Conversely, no significant association was observed between PA and abdominal AA (OR = 1.013; 95% CI = 0.993-1.034; P = .210). There was no heterogeneity and horizontal pleiotropy in the MR analyses (P > .05). PA is genetically and causally associated with higher risks of AA and AD. More attention should be paid to the screening and treatment of PA to reduce the incidence of aortic diseases.

摘要

新出现的研究表明,原发性醛固酮增多症(PA)与主动脉瘤(AA)/主动脉夹层(AD)之间可能存在致病重叠。尽管病例报告提示PA与AA/AD之间可能存在联系,但这种关系的因果性仍不明确。本研究首次通过孟德尔随机化(MR)分析阐明基因预测的PA与AA和AD风险之间的因果关联。从公开可用的全基因组关联研究汇总统计数据中识别出与PA相关的全基因组显著单核苷酸多态性。从芬兰基因数据库中获取与AA和AD的遗传关联。采用逆方差加权(IVW)方法以及互补的MR分析方法来生成主要估计值。进行敏感性分析以确保研究结果的稳健性。利用IVW方法的MR分析显示,基因预测的PA与AA风险(OR = 1.038;95%CI = 1.024 - 1.053;P <.01)、胸主动脉瘤(OR = 1.066;95%CI = 1.045 - 1.087;P <.01)和AD风险(OR = 1.165;95%CI = 1.113 - 1.219;P <.01)之间存在显著因果关联。相反,未观察到PA与腹主动脉瘤之间存在显著关联(OR = 1.013;95%CI = 0.993 - 1.034;P =.210)。MR分析中不存在异质性和水平多效性(P >.05)。PA在基因上与AA和AD的较高风险存在因果关联。应更加关注PA的筛查和治疗,以降低主动脉疾病的发病率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d08/11936671/80bb889a7548/medi-104-e41951-g001.jpg

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