Paraoxonase1 polymorphism Leu-Met55 is associated with cerebral infarction in Japanese population

Paraoxonase1 (PON1) is HDL-associated ester hydrolase which has been shown to prevent LDL and HDL oxidation in vitro. PON1-coding region has two common polymorphisms (M/L55 and A/B192) that influence PON activity. We examined whether these polymorphisms relates with the incidence of cerebral infarction (CI) which is one of the major atherosclerotic disease in Japan.

The study population was comprised of 112 unrelated Japanese CI patients and 106 healthy Japanese individuals. The PON1 genotypes were determined by PCR and digestion by specific restriction enzymes.

PON1-192 polymorphism revealed no significant difference of genotype and allelic distribution in CI patients and controls. Frequency of L/M alleles in PON1-55 polymorphism (0.88, 0.12, respectively) was different from previously reported frequencies in Caucasians. Comparison of allelic distribution of the PON1-55 polymorphism showed a significant increase of the M allele in CI subjects compared with control subjects. All three subjects with the MM genotype were in the CI group. Of subjects with an AA genotype, the frequencies of the MM and LM genotypes were significantly higher and that of the LL genotype was significantly lower in the CI group compared with the control group. Frequency of the M allele in the CI group was significantly higher in subjects who had the AA genotype.

These findings suggest that the enzyme might be involved in the development of atherosclerosis of cerebral arteries. Moreover, this finding might indicates that the genetic markers in Japanese linked to distinct genetic event from Caucasians.