Qiu Shi, Liu Zhen, Wang Chun-Ting, Sun Xiao-di, Liu Zeng-Qiang, Liu Wen
Department of Cardiac Surgery, The Second Hospital of Shandong University, Jinan, Shandong, China.
Department of Cadre Health Care, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, Shangdong, 250033, People's Republic of China.
Nutr Metab (Lond). 2024 Sep 20;21(1):75. doi: 10.1186/s12986-024-00853-5.
3-Hydroxybutyrate, also called β-hydroxybutyrate, is a significant constituent of ketone bodies. Previous observational and experimental studies have suggested that ketogenic diet, especially 3-hydroxybutyrate, may have a protective effect against cardiovascular disease. However, the relationship between ketone bodies, especially 3-hydroxybutyrate, and aortic dissection remains uncertain.
Publicly accessible data from genome-wide association study (GWAS) was utilized to obtain information on ketone bodies, including 3-hydroxybutyrate, acetoacetate and acetone as exposure respectively, while GWAS data on aortic dissection was used as outcome. Subsequently, two-sample Mendelian randomization (MR) analysis was conducted to examine the potential relationship between ketone bodies and aortic dissection. Then, reverse and multivariate Mendelian randomization analyses were performed. Additionally, sensitivity tests were conducted to assess the robustness of MR study.
The inverse-variance weighted (IVW) method of Mendelian randomization analysis of gene prediction observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection (OR 0.147, 95% CI 0.053-0.410). Furthermore, consistent findings were obtained through the implementation of the weighted median, simple mode, Mendelian randomization-Egger (MR-Egger), and weighted mode methods. After adjusting acetoacetate (OR 0.143, 95% CI 0.023-0.900) or acetone (OR 0.100, 95% CI 0.025-0.398), MR analysis of gene prediction still observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection. No indications of heterogeneity or pleiotropy among the SNPs were detected.
The findings from the MR analysis demonstrated that genetically predicted 3-hydroxybutyrate exhibits a protective effect against aortic dissection.
3-羟基丁酸，也称为β-羟基丁酸，是酮体的重要组成部分。先前的观察性和实验性研究表明，生酮饮食，尤其是3-羟基丁酸，可能对心血管疾病具有保护作用。然而，酮体，尤其是3-羟基丁酸，与主动脉夹层之间的关系仍不确定。
利用全基因组关联研究（GWAS）的公开数据，分别获取有关酮体的信息，包括3-羟基丁酸、乙酰乙酸和丙酮作为暴露因素，而将主动脉夹层的GWAS数据作为结果。随后，进行两样本孟德尔随机化（MR）分析，以检验酮体与主动脉夹层之间的潜在关系。然后，进行反向和多变量孟德尔随机化分析。此外，进行敏感性测试以评估MR研究的稳健性。
基因预测的孟德尔随机化分析的逆方差加权（IVW）方法观察到3-羟基丁酸与主动脉夹层风险之间存在负相关（OR 0.147，95%CI 0.053-0.410）。此外，通过加权中位数、简单模式、孟德尔随机化-Egger（MR-Egger）和加权模式方法的实施获得了一致的结果。在调整乙酰乙酸（OR 0.143，95%CI 0.023-0.900）或丙酮（OR 0.100，95%CI 0.025-0.398）后，基因预测的MR分析仍观察到3-羟基丁酸与主动脉夹层风险之间存在负相关。未检测到单核苷酸多态性（SNP）之间存在异质性或多效性的迹象。
MR分析的结果表明，基因预测的3-羟基丁酸对主动脉夹层具有保护作用。
