Increased Risk of Heart Attack Linked To Polymorphism in the 5HTR2C Serotonin Receptor Gene

serotonin SNP

In the December 2013 issue of PLOS One, a research team from the Department of Psychiatry, Duke University Medical Center, Durham, NC reports that a functional polymorphism of the 5HTR2C gene is associated with a 38% increased risk for cardiovascular disease events. This includes mortality and myocardial infarction (MI), independent of several traditional risk factors, and over a 7-year follow-up period.

In 2012, the same research group found that a functional polymorphism in the 5HTR2C Gene is linked to enhanced stress-induced cortisol response.

Cortisol, produced by the adrenal glands’ cortex is the end-product of the HPA axis activation, and a major stress hormone.

Psychological stress, anger, hostility, depression and social isolation are well-known factors contributing to the pathogenesis and course of cardiovascular diseases, especially myocardial infarction (MI).

The neurotransmitter serotonin is involved in the regulation of the stress response, and it acts at multiple levels in the brain or periphery to facilitate the stress-induced hypothalamic–pituitary–adrenal (HPA) axis activation.

In particular, the serotonin 5HTR2C receptor is among the key modulators of HPA axis, a major branch of the stress system. Signaling through the 5HTR2C receptor drives HPA axis activation mainly through the increase of corticotropin releasing hormone (CRH) release in the hypothalamic paraventricular nucleus.

The authors of the PLOS One study discuss the possible interactions between 5HT2C receptors, HPA axis activity, and levels of cortisol, anger, hostility and depression, and moreover, how these factors may contribute to inflammation, particularly related to unstable atherosclerotic plaques in the coronary arteries.

According to the authors, if replicated in other studies, these findings may indicate that behavioral and pharmacologic interventions to reduce HPA axis hyper-reactivity in individuals that are carriers of this polymorphism may become useful approach to improve prognosis and/or provide primary prevention from MI.

Source: PLoS One, 2013, 18;8(12):e82781. doi: 10.1371/journal.pone.0082781.
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