| Title: | Interplay Between Plasma Glycine and Branched-Chain Amino Acids Contributes to the Development of Hypertension and Coronary Heart Disease |
| Journal: | Hypertension |
| Published: | 8 Apr 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38587181/ |
| DOI: | https://doi.org/10.1161/hypertensionaha.123.22649 |
| URL: | https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.123.22649 |
Publication 9942
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Abstract
BACKGROUND: 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.</p>
METHODS: 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. P-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.</p>
RESULTS: 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 (P-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).</p>
CONCLUSIONS: 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.</p>
4 Authors
- Mateusz Dziedzic
- Ewelina Józefczuk
- Tomasz J. Guzik
- Mateusz Siedlinski
1 Application
| Application ID | Title |
|---|---|
| 93156 | Biomarkers, immunological signatures and hypertension-associated diseases - causal inference using genetic and observational approaches |
Enabling scientific discoveries that improve human health