Genetic variation in paraoxonase-1 and paraoxonase-2 is associated with variation in plasma lipoproteins in Alberta Hutterites.

In a sample taken from the genetically isolated Alberta Hutterites, we previously found that PON1 variation was associated with variation in plasma lipoprotein traits, including LDL and HDL cholesterol. With the recent cloning of the PON1-related gene PON2, we undertook studies of the association between genetic variation in PON2 and variation in plasma quantitative traits variation in a sample of 745 Alberta Hutterites. We found novel genetic associations between PON2 variation and variation in fasting plasma concentrations of total cholesterol and apolipoprotein AI. We confirmed our previously observed significant associations in this study sample between PON1 genetic variation and variation in plasma apo B-related traits, such as LDL, non-HDL and HDL cholesterol and apo B itself. Furthermore, there was almost complete linkage disequilibrium between PON2 alleles G148 and C311. We found no association between PON2 variation and plasma glucose or insulin. Taken together, our results suggest that common genetic variation on chromosome 7q21.3-22.1 in both PON1 and PON2 that affects the amino acid sequence of the respective gene products is associated with significant variation in intermediate traits in plasma lipoprotein metabolism.