The Role of Glycine Metabolism in Coronary Artery Disease

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Figure 1
Association of Serum Glycine Levels with Risk of CAD in the UK Biobank. Individuals in the highest quintile of glycine levels had significantly reduced risk of prevalent CAD (OR = 0.76, 95% CI 0.67–0.87; p < 0.0001) (A) and incident CAD (HR = 0.70, 95% CI 0.65–0.77; p < 0.0001) (B) compared to individuals in the first quintile. p-value for trend for association with risk of prevalent CAD (A) and log-rank p-value for association with incident risk of CAD (B) across quintiles are also shown, including the number of subjects at risk of incident CAD in each quintile at baseline and the indicated follow-up time (bottom panel in B).

Exploring the Role of Glycine Metabolism in Coronary Artery Disease: Insights from Human Genetics and Mouse Models (2025)

Results: Among 105,718 UK Biobank subjects, elevated serum glycine levels were associated with significantly reduced risk of prevalent CAD (Quintile 5 vs. Quintile 1 OR = 0.76, 95% CI 0.67–0.87; p < 0.0001) and incident CAD (Quintile 5 vs. Quintile 1 HR = 0.70, 95% CI 0.65–0.77; p < 0.0001) after adjustment for age, sex, ethnicity, anti-hypertensive and lipid-lowering medications, blood pressure, kidney function, and diabetes. A GWAS meta-analysis with 230,947 subjects identified 61 loci for glycine levels, of which 26 were novel. MR analyses provided modest evidence that genetically elevated glycine levels were causally associated with reduced systolic blood pressure and risk of type 2 diabetes, but did not provide significant evidence for an association with decreased risk of CAD. Glycine supplementation in mice had no effects on cardiometabolic traits or atherosclerotic lesion development.

Conclusions: While expanding the genetic architecture of glycine metabolism, MR analyses and in vivo feeding studies did not provide evidence that the clinical association of this amino acid with atherosclerosis represents a causal relationship.