Sun Yaodong, Du Dongdong, Zhang Jiantao, Zhao Linlin, Zhang Bufan, Zhang Yi, Song Tianxu, Wu Naishi
Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Department of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Front Cardiovasc Med. 2024 Jul 22;11:1382702. doi: 10.3389/fcvm.2024.1382702. eCollection 2024.
This Mendelian randomization (MR) study aimed to explore the causal relationship between the genetic predisposition to type 2 diabetes mellitus (T2DM) and aortic dissection (AD), and to assess associations with genetically predicted glycemic traits. The study sought to verify the inverse relationship between T2DM and AD using a more robust and unbiased method, building on the observational studies previously established.
The study employed a two-sample and multivariable MR approach to analyze genetic data from the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) with 74,124 cases and 824,006 controls, and the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) involving up to 196,991 individuals. For AD data, FinnGen Release 10 was used, including 967 cases and 381,977 controls. The research focused on three foundational MR assumptions and controlled for confounders like hypertension. Genetic instruments were selected for their genome-wide significance, and multiple MR methods and sensitivity analyses were conducted.
The study revealed no significant effect of genetic predisposition to T2DM on the risk of AD. Even after adjusting for potential confounders, the results were consistent, indicating no causal relationship. Additionally, glycemic traits such as fasting glucose, fasting insulin, and HbA1c levels did not show a significant impact on AD susceptibility. The findings remained stable across various MR models and sensitivity analyses. In contrast, genetic liability to T2DM and glycemic traits showed a significant association with coronary artery disease (CAD), aligning with the established understanding.
Contrary to previous observational studies, this study concludes that genetic predisposition to T2DM does not confer protection against AD. These findings underscore the imperative for further research, particularly in exploring the preventative potential of T2DM treatments against AD and to facilitate the development of novel therapeutic interventions.
本孟德尔随机化（MR）研究旨在探讨2型糖尿病（T2DM）的遗传易感性与主动脉夹层（AD）之间的因果关系，并评估与遗传预测的血糖特征的关联。该研究试图在先前已开展的观察性研究基础上，使用更稳健且无偏倚的方法来验证T2DM与AD之间的反向关系。
本研究采用两样本多变量MR方法，分析来自跨种族关联研究的糖尿病荟萃分析（DIAMANTE）的遗传数据，该分析包含74,124例病例和824,006例对照，以及葡萄糖和胰岛素相关性状联盟（MAGIC）的荟萃分析，涉及多达196,991人。对于AD数据，使用了芬兰基因库发布的第10版数据，包括967例病例和381,977例对照。该研究聚焦于三个基本的MR假设，并对高血压等混杂因素进行了控制。基于全基因组显著性选择遗传工具，并进行了多种MR方法和敏感性分析。
该研究表明，T2DM的遗传易感性对AD风险无显著影响。即使在调整潜在混杂因素后，结果依然一致，表明不存在因果关系。此外，空腹血糖、空腹胰岛素和糖化血红蛋白水平等血糖特征对AD易感性也未显示出显著影响。在各种MR模型和敏感性分析中，研究结果均保持稳定。相比之下，T2DM的遗传易感性和血糖特征与冠状动脉疾病（CAD）存在显著关联，这与已有的认识相符。
与先前的观察性研究相反，本研究得出结论，T2DM的遗传易感性并不能预防AD。这些发现凸显了进一步研究的必要性，特别是在探索T2DM治疗对AD的预防潜力以及促进新型治疗干预措施的开发方面。
