Patients with Down syndrome appear to be protected from the development of atherosclerosis. On the contrary, hyperhomocysteinemia is associated with an increased risk for atherosclerosis. As hyperhomocysteinemia due to cystathionine beta synthase deficiency is associated with a decreased expression of paraoxonase-1, a major anti-atherosclerotic component secreted by the liver, we aimed to analyze the expression of paraoxonase-1 and cystathionine beta synthase in Down syndrome fetal liver by quantitative real-time reverse transcriptase-polymerase chain reaction. Paraoxonase-1 was up-regulated in Down syndrome fetal liver, while cystathionine beta synthase gene expression in Down syndrome fetuses was similar to the gene level in control fetuses. Moreover, there was no evidence for an association between paraoxonase-1 genotypes influencing paraoxonase-1 gene expression and Down syndrome. Since most serum paraoxonase-1 is synthesized in the liver, an increase of hepatic paraoxonase-1 expression might be one of the factors which could explain the low incidence of atherosclerotic vascular disease in Down syndrome.