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HDL Gene Affects Risk of Death and Adverse Cardiac Events

Paraoxonse 1 gene variants, activity linked to oxidative stress and cardiovascular risk

TUESDAY, March 18 (HealthDay News) -- Patients who carry the Q192R polymorphism of the paraoxonase 1 (PON1) gene -- which is associated with high-density lipoprotein (HDL) -- may have an increased risk of death and major adverse cardiac events. Those with the lowest PON1 activity may also have a significantly higher risk of major adverse cardiac events, according to research published in the March 19 issue of the Journal of the American Medical Association.

Tamali Bhattacharyya, M.D., of the Cleveland Clinic in Cleveland, Ohio, and colleagues genotyped 1,399 patients who underwent coronary angiography between September 2002 and November 2003 and followed them through December 2006. They identified the QQ192 genotype in 46.3 percent of patients, the QR192 genotype in 43.9 percent and the RR192 genotype in 9.8 percent.

The researchers found that the risk of all-cause mortality and major adverse cardiac events was significantly higher in subjects with the QQ192 genotype than in those with the QR192 and RR192 genotypes (adjusted hazard ratios, 2.05 and 1.48, respectively). They also found that the incidence of major adverse cardiac events was significantly lower in subjects in the highest PON1 activity quartile than in those in the lowest PON1 activity quartile (7.3 percent versus 25.1 percent for paraoxonase, and 7.7 percent versus 23.5 percent for arylesterase).

"Paraoxonase 1 is almost exclusively found to be associated with HDL particles within the circulation and has been argued to promote some of the anti-inflammatory and antioxidant effects attributed to HDL," the authors conclude. "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."

Several study authors report financial relationships with the pharmaceutical industry.

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