Discordance in human paraoxonase-1 gene between phenotypes and genotypes in chronic kidney disease

Human serum paraoxonase-1 (PON1) is a high-density lipoprotein-associated ester hydrolase which can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect. Two common polymorphisms are known in the PON1 gene in humans (at positions 55 and 192), from which the latter gene alteration has been mainly attributed to alter the activity of the protein. Moreover, significantly reduced PON1 activity was found in chronic kidney disease (CKD) and renal transplant patients.

The aim of the present study was to investigate the genotype and phenotype distribution of the PON1 gene as well as its end product activity in patients with CKD (n = 117), in renal transplant recipients (n = 146) and in reference subjects (n = 1,180).

Unexpectedly high discordances between phenotype and genotype assessments were observed in all studied groups (28.2% in the CKD, 20.55% in the transplant and 30.9% in the reference group). Arylesterase activity was significantly lower in the CKD group compared to the reference sample. There were no significant differences between patients and the reference group in the frequencies of polymorphisms PON1-55 and PON1-192. PON1 activity did not differ in patients compared to the reference group.

Both PON1 phenotype and genotype determinations are necessary to estimate PON1 status.