Department of Internal Medicine (M.D., E.J., T.J.G., M.S.), Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland.
Center for Medical Genomics OMICRON (T.J.G., M.S.), Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland.
Hypertension. 2024 Jun;81(6):1320-1331. doi: 10.1161/HYPERTENSIONAHA.123.22649. Epub 2024 Apr 8.
Higher levels of plasma glycine are linked to a reduced risk, while increased levels of total branched-chain amino acids (tBCAAs) are associated with a higher risk of essential hypertension and coronary heart disease (CHD). As these metabolic components are interconnected, analyzing the tBCAAs/glycine ratio may help to understand their interplay in the pathogenesis of cardiovascular disease.
The Cox regression approach was combined with the development of novel genetic tools for assessments of associations between plasma metabolomic data (glycine, tBCAAs, and tBCAAs/glycine ratio) from the UK Biobank and the development of hypertension and CHD. Genome-wide association study was performed on 186 523 White UK Biobank participants to identify new independent genetic instruments for the 2-sample Mendelian randomization analyses. -gain statistic >10 identified instruments associated with tBCAAs/glycine ratio significantly stronger compared with individual amino acids. Outcomes of genome-wide association study on hypertension and CHD were derived from the UK Biobank (nonoverlapping sample), FinnGen, and CARDIoGRAMplusC4D.
The tBCAAs/glycine ratio was prospectively associated with a higher risk of developing hypertension and CHD (hazard ratio quintile Q5 versus Q1, 1.196 [95% CI, 1.109-1.289] and 1.226 [95% CI, 1.160-1.296], respectively). Mendelian randomization analysis demonstrated that tBCAAs/glycine ratio (-gain >10) was a risk factor for hypertension (meta-analyzed inverse-variance weighted causal estimate 0.45 log odds ratio/SD (95% CI, 0.26-0.64) and CHD (0.48 [95% CI, 0.29-0.67]) with an absolute effect significantly larger compared with the effect of glycine (-0.06 [95% CI, -0.1 to -0.03] and -0.08 [95% CI, -0.11 to -0.05], respectively) or tBCAAs (0.22 [95% CI, 0.09-0.34] and 0.12 [95% CI, 0.01-0.24], respectively).
The total BCAAs/glycine ratio is a key element of the metabolic signature contributing to hypertension and CHD, which may reflect biological pathways shared by glycine and tBCAAs.
血浆甘氨酸水平升高与降低患原发性高血压和冠心病（CHD）风险有关，而总支链氨基酸（tBCAAs）水平升高与患原发性高血压和冠心病风险升高有关。由于这些代谢成分相互关联，分析 tBCAAs/甘氨酸比值可能有助于了解它们在心血管疾病发病机制中的相互作用。
采用 Cox 回归方法，结合新型遗传工具，评估英国生物银行血浆代谢组学数据（甘氨酸、tBCAAs 和 tBCAAs/甘氨酸比值）与高血压和 CHD 发生之间的关联。对 186523 名白人英国生物银行参与者进行全基因组关联研究，以确定用于 2 样本孟德尔随机化分析的新的独立遗传工具。-gain 统计量>10 表明与个体氨基酸相比，tBCAAs/甘氨酸比值与更显著相关。高血压和 CHD 的全基因组关联研究结果来自英国生物银行（非重叠样本）、芬兰基因组研究和 CARDIOGRAMplusC4D。
tBCAAs/甘氨酸比值与高血压和 CHD 的发病风险呈正相关（Q5 与 Q1 相比，危险比五分位数为 1.196[95%CI，1.109-1.289]和 1.226[95%CI，1.160-1.296]）。孟德尔随机化分析表明，tBCAAs/甘氨酸比值（-gain>10）是高血压的危险因素（荟萃分析逆方差加权因果估计 0.45 个对数优势比/SD（95%CI，0.26-0.64）和 CHD（0.48[95%CI，0.29-0.67]），其绝对效应明显大于甘氨酸（-0.06[95%CI，-0.1 至-0.03]）或 tBCAAs（0.22[95%CI，0.09-0.34]和 0.12[95%CI，0.01-0.24]）的效应。
tBCAAs/甘氨酸比值是导致高血压和 CHD 的代谢特征的关键因素，这可能反映了甘氨酸和 tBCAAs 之间共享的生物学途径。
