Genetic variaton affects assocation of amino acids to risk of myocardial infarction

A patient’s genetic background could be of importance for how the one-carbon metabolism affects the development of coronary heart disease.

PhD candidate Yunpeng Ding has studied how plasma levels of the amino acids serine and glycine relate to risk of myocardial infarction in patients with suspected angina pectoris. Serine and glycine are components within the intricate one-carbon metabolism. The results indicate different effects in patients with different genetic background. The work is based on data from the WENBIT Study, which originally investigated the effects of various B-vitamin supplements in more than 4100 angina patients.

Higher levels of glycine, but not serine, were associated with decreased risk of acute myocardial infarction in the population as a whole. However, the associations were influenced by genetic variation of the MTHFD1 gene. MTHFD1 is an enzyme catalyzing reactions in the one-carbon metabolism. Low plasma glycine showed stronger risk relationship in carriers of the CC genotype of the functional polymorphism rs1076991, and weaker associations in patients carrying the minor T-allele. Also, both low plasma serine and glycine were associated with an increased risk among patients carrying the rs2236225 minor A-allele.

Furthermore, Ding and colleagues show that patients carrying the rs1076991 minor T-allele have higher risk of myocardial infarction than carriers of the CC genotype. This association was dependent on B vitamin supplementation, and most pronounced in the group of patients randomly allocated to treatment with both vitamin B6, folic acid (B9) and B12.

Overall, the results underline the importance of looking at both genes and diet when evaluating one-carbon metabolism related mechanisms that could lead to cardiovascular disease.


Thesis: MTHFD1 and relevant biomarkers in cardiovascular disease – Observational studies in patients with suspected stable angina pectoris in Norway
 Yunpeng Ding
Time and place: March 24, 2017, University of Bergen


Ding, Y., Svingen, G. F., Pedersen, E. R., Gregory, J. F., Ueland, P. M., Tell, G. S., & Nygaard, O. K. (2016). Plasma glycine and risk of acute myocardial infarction in patients with suspected stable angina pectoris. Journal of the American Heart Association, 5(1), e002621.

Ding, Y. P., Pedersen, E. K. R., Johansson, S., Gregory, J. F., Ueland, P. M., Svingen, G. F. T., Helgeland, Ø., Meyer, K., Fredriksen, Å., & Nygård, O. K. (2016). B vitamin treatments modify the risk of myocardial infarction associated with a MTHFD1 polymorphism in patients with stable angina pectoris. Nutrition, Metabolism and Cardiovascular Diseases, 26(6), 495-501.

Ding, Y., Pedersen, E. R., Svingen, G. F., Helgeland, Ø., Gregory, J. F., Løland, K. H., Meyer, K., Tell, G. S., Ueland, P. M., & Nygård, O. K. (2016). MTHFD1 Polymorphisms Modify the Associations of Plasma Glycine and Serine with Risk of AMI in Patients with Stable Angina Pectoris in WENBIT. Circulation: Cardiovascular Genetics, CIRCGENETICS-116.

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