We report studies of the association between genetic variation in PON2 and variation in plasma quantitative traits in a sample of 334 non-diabetic Oji-Cree. We detected associations between PON2 variation in codon 148 (Ala --> Gly) and variation in fasting plasma concentrations of total and low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B. In particular, homozygotes for a PON2 allele that encoded A148 had significantly higher plasma total, LDL cholesterol and apo B than subjects having the other two genotypes (p < 0.01). Taken together, our results suggest that common genetic variation on chromosome 7q21.3-22.1 in PON2 is associated with significant variation of intermediate traits in plasma lipoprotein metabolism.