Medical Center

NEW YORK (Reuters Health) Oct 07 – Paraoxonase (PON)-1 variants influence the long-term risk of fatal complications from coronary artery disease in men, Dutch researchers report in the September 29th issue of the Journal of the American College of Cardiology. Dr. J. Wouter Jukema at Leiden University Medical Center and colleagues observe that PON-1, a detoxifying esterase with antioxidant properties, is a potential cardiovascular risk reduction target.

PON-1 knockout models have shown higher susceptibility to atherosclerosis, and PON activity contributes to cardiovascular risk in humans.

To examine whether gene variants associated with PON might influence outcome, the researchers conducted a follow-up study of 793 non-diabetic men with coronary artery disease who had been enrolled between 1989 and 1993 in a two-year trial of statin therapy.

Using data from nationwide registries, the authors found that carriers of the PON-1 M55 allele had a considerably increased risk of cardiovascular complications, compared with L55 carriers. For example, the 10-year absolute risk of death from ischemic heart disease was 4.6% in L55 homozygote patients, 7.1% for heterozygotes and 10.9% for M55 homozygotes.

The M55 allele, seen in 37% of the studied group as well as in other Caucasian samples, thus conferred a hazard ratio of 1.56 for such death. However, it had no effect on all-cause mortality.

Similarly, an elevated risk was found in carriers of the 192Q isotype of PON-1. The hazard ratio per allele copy was 1.71. Again, no association was seen with overall mortality.

Both M55 and 192Q isotypes, the researchers observe, have previously been associated with lower PON activity.

In comments to Reuters Health, Dr. H. Robert Superko, author of an accompanying editorial, pointed out that the new information about PON-1 “is very relevant for the 14% of the population that has two copies of the variant.”

Dr. Superko, from Celera Inc. Genetics in Alameda, California, also commented that “unlike some genetic variants, such as KIF6, that identify response to statin drug treatment, how to use this PON-1 genetic information to determine treatment is less clear.”