Paraoxonase Polymorphisms and Leukoaraiosis

Shin, Byoung Soo

Abstract

BACKGROUND
There is an inverse relationship between lesion extent and plasma levels of antioxidants for white-matter lesions (leukoaraiosis) that are visible on MRI. Paraoxonase (PON) has both antioxidative and antiatherosclerotic potential, and could thus protect against both macrovascular and microvascular disease. The PON1 gene has two common polymorphisms in the coding region at positions 192 (Q192R) and 55 (M55L); the PON2 gene also has two common polymorphisms in the coding region at positions 148 (G148A) and 311 (C311S). We evaluated the associations between PON polymorphisms and leukoaraiosis, and investigated the role of PON polymorphisms in the lipid profile in leukoaraiosis.
METHODS
A total of 745 subjects was genotyped for the PON1 M55L, PON1 Q192R, PON2 G148A, and PON2 C311S polymorphisms using melting-point analysis with LightCycler real-time PCR technology. Leukoaraiosis was graded into absent, punctuate, early confluent, and confluent abnormalities using 1.5-T superconducting magnets with T2-weighted and fluid-attenuated inversion-recovery sequences.
RESULTS
The severity of leukoaraiosis was correlated with hypertension, advanced age, homocysteine, and serum C-reactive protein (p<0.05). The genotype and allele distribution of the PON polymorphisms did not differ significantly between the leukoaraiosis and control subjects. We found that PON1 55 LL genotype was correlated with high serum concentrations of lipoprotein A (p<0.05). The PON2 148 GG and PON2 311 SS genotypes were correlated with high serum concentrations of cholesterol, apolipoprotein B, and low-density lipoprotein (p<0.05).
CONCLUSIONS
No association was found between PON gene polymorphisms and leukoaraiosis. Leukoaraiosis can be influenced by the PON1 55 LL, PON2 148 GG, and PON2 311 SS genotypes, which affect the serum concentration of lipoprotein.