Study Links Protein To Risk Of Heart Disease

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