Study Links Protein To Risk Of Heart Disease

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Main Category: Heart Disease
Also Included In: Genetics;  Cholesterol
Article Date: 18 Mar 2008 - 7:00 PST

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A new study published in the Journal of the American Medical Association reports that there is an association between the gene for the HDL-associated protein paraoxonase 1 (PON1) and adverse cardiac events such as coronary artery disease. Researcher Stanley L. Hazen, M.D., Ph.D (Cleveland Clinic) and colleagues also find that variations in both the PON1 gene and its enzyme activity may increase the likelihood of cardiovascular disease events.

It has been believed that in animals, the PON1 gene prevents atherosclerosis (multiple plaques that harden the arteries). However, researchers have not found a similar cardio-protective role in humans. Current literature does suggest, though, that it is possible for PON1 to have antioxidant and cardio-protective properties.

Dr. Hazen and colleagues decided to investigate PON1 activity - anti-inflammatory and antioxidant activities - and a PON1 polymorphism (gene variation) Q192R in order to see if there is an association with higher rates of cardiovascular disease, heart attack, stroke or death. They studied 1,399 patients who elected to undergo diagnostic coronary angiography from September 2002 to November 2003. Participants were followed-up until the end of 2006.

Hazen and colleagues found that participants in the highest PON1 activity quartile (7.3% for paraoxonase) were significantly less likely to have major adverse cardiac events compared to those in the lowest activity quartile (25.1% for paraoxonase).

A second result of the study found that there were significant dose-dependent associations for PON1 polymorphisms, with decreased levels of serum PON1 activity and increased levels of oxidative stress (damage to cells and tissues when the levels of free radicals and antioxidants are not balanced.) Over the 3-year period after study enrollment, the authors found an association between ailments such as coronary artery disease and other adverse cardiovascular events and the PON1 Q192R polymorphism and serum PON1 activity.

The researchers conclude: "The current findings provide direct prospective evidence of an important mechanistic link between the PON1 gene and PON1 systemic activity measures with both multiple quantitative indices of oxidative stress and atherosclerotic heart disease development in humans. Paraoxonase 1 is [strongly] associated with HDL particles within the circulation and has been argued to promote some of the anti-inflammatory and antioxidant effects attributed to HDL. Thus, the present studies also provide further support for the concept that functional properties beyond the ability of HDL and its associated proteins to promote reverse cholesterol transport contribute to the overall ability of this lipoprotein to reduce or prevent development of atherosclerosis."

Stanley L. Hazen, et al.
JAMA (2008). 299[11]:1265-1276.
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Written by: Peter M Crosta
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