Future studies of low-activity PON1 phenotype subjects may reveal how PON1 protects against cardiovascular disease.

The article by Jarvik et al, 1 appearing in this issue, illustrates the pros and cons of using a large panel of SNPs for probing deeper into the association between serum paraoxonase (PON1) and vascular disease. The obvious advantages of using such a series of convenient genetic markers are somewhat compromised in this instance by the presence of several, long-ago established recombination sites within the human PON1 genetic sequence. Appreciable linkage disequilibrium (LD) exists within conserved segments for short stretches of the PON1 gene, so that representative residues from several of these contiguous segments constitute distinctive haplotypes. However, Jarvik et al1 have found that none of these genetic markers show any high degree of association with cardiovascular disease. The authors conclude that finding a reduced level of serum PON1 enzymatic activity still seems to be the best indicator of some important relationship between the serum PON1 enzyme and cardiovascular disease.