New research suggests smoking cigarettes increases the risk of suffering a heart attack by activating a gene that affects blood clotting. The gene F2RL3 is expressed on platelets and codes for a protein called PAR4, which is involved in platelet activation.
Smoking causes changes to DNA methylation, which is the mechanism used in many cells to control gene expression. DNA methylation changes the properties of DNA without making changes to the actual DNA sequence and is reversible. DNA hypomethylation at the F2RL3 locus has previously been associated with smoking and atherosclerotic cardiovascular, although it was not known whether the smoking-related changes formed a pathway to disease.
The study took a multidisciplinary approach involving four different study designs and included data from the Children of the 90s longitudinal study. The researchers analyzed smoking-related changes to the F2RL3 gene and determined smoking reduces DNA methylation in the gene, which in turn causes changes to platelet reactivity, which can increase the risk of myocardial infarction.
“Smoking-induced epigenetic DNA hypomethylation at F2RL3 appears to increase PAR4 expression with potential downstream consequences for platelet reactivity,” wrote the researchers. “Combined evidence here not only identifies F2RL3 DNA methylation as a possible contributory pathway from smoking to cardiovascular disease risk but from any feature potentially influencing F2RL3 regulation in a similar manner.”
The researchers note that the changes to the gene caused by smoking appear to be reversible; however, it can take several years after a person gives up smoking for the levels to return to normal, so the increased risk of myocardial infarction could well continue for several years after an individual quits smoking.
“There are other genetic and non-genetic factors that can affect DNA methylation in a similar way, and this means that our findings could also be relevant beyond smoking,” said Dr. Laura Corbin, Research Fellow, Bristol Medical School (PHS) and lead author of the study. “If verified, our findings may also have implications for the effectiveness of recently approved drugs designed to target the platelet protein PAR4.”
You can read more about the study in the paper – Epigenetic Regulation of F2RL3 Associates with Myocardial Infarction and Platelet Function – which was recently published in the Circulation Research. DOI: 10.1161/CIRCRESAHA.121.318836.