Paraoxonase Polymorphisms and the Risk of Arterial Ischemic Stroke among Young Adults
Despite extensive investigation, the etiology of arterial ischemic stroke (AIS) in the young remains unknown in one-third of patients. Serum paraoxonase (PON) is an HDL-associated esterase that hydrolyzes products of lipid peroxidation and prevents the oxidation of LDL, thus exerting anti-oxidant and anti-atherogenic effects. PON levels have been shown to be significantly reduced in patients with coronary artery disease. Two common polymorphisms in the PON gene, the 55 Leu (L allele)→ Met (M allele) and the 192 Gln (A allele)→ Arg (B allele) substitutions, influence PON activity in a gene-dose dependent manner. As the association of these polymorphisms with cardiovascular disease and stroke is controversial, we investigated their role in a young population with AIS. We carried out a cross-sectional study including 138 patients (84 women, 54 men; mean age: 32.9 years) with a first AIS before the age of 45 years and 102 age-matched controls. The diagnosis of AIS was based on clinical and neuroimaging findings. Fragments of the coding region of the PON gene encompassing the 192 and 55 polymorphisms were analyzed by PCR amplification and posterior restriction endonuclease digestion. Among patients, 17.4% were found to be homozygous and 46.4% heterozygous for the B allele at position 192, compared to 8.8% and 38.3% respectively among controls. This yielded a significantly higher allele frequency of the 192 B allele among patients than controls: 0.406 vs. 0.279, P=0.0056, OR=1.76 (CI=1.17–2.65). Regarding the PON 55 L allele, there was no significant difference between patients and controls (P=0.59). The presence of hyperlipidemia, diabetes mellitus and smoking, factors known to influence PON levels, were analyzed in the patient and control groups and did not significantly alter the difference in allele frequencies. These findings suggest that the PON 192 B allele is associated with an increased risk of AIS among young adults. However, studies including a larger number of patients and analyzing the effect of PON on atherosclerosis are necessary to better understand the role of these observations in the development of AIS in the young.