The paraoxonase PON1 promoter polymorphism C(-107)T is associated with increased serum glucose concentrations in non-diabetic patients

Aims/hypothesis. Oxidative stress could contribute to diabetes and its comp lications by predisposing to insulin resistance. Lipid peroxidation product s are thought to be one mechanism involved in reduced insulin sensitivity. The serum enzyme, paraoxonase-1, protects lipoprotein lipids from oxidation . We examined the hypothesis that paraoxonase-1 could be associated with ab normal serum glucose concentrations in non-diabetic patients. Methods. Serum paraoxonase-1 activities and concentrations, as well as para oxonase-1 gene polymorphisms, were analysed as a function of fasting glucos e concentrations in non-diabetic patients and in Type II (non-insulin-depen dent) diabetic patients. Results. Serum paraoxonase-1 activities and concentrations were lower (p < 0.05) in non-diabetic patients with abnormal fasting glucose concentrations . It was due to a higher frequency of low expressor paraoxonase-1 promoter genotypes in patients with abnormal glucose control. Promoter polymorphisms were independent determinants of abnormal fasting glucose concentrations. Low expressor genotypes were associated with higher glucose concentrations in non-diabetic patients (p = 0.046) and a trend to higher concentrations i n Type II diabetic patients. The coding region paraoxonase-1 polymorphisms L55 M and Q192R was not associated with differences in fasting glucose. Conclusion interpretation. The promoter polymorphism C(-107)T is a marker f or abnormal fasting glucose concentrations in non-diabetic patients. It cou ld indicate an active role for paraoxonase-1, possibly pre-disposing to ins ulin resistance, or linkage of paraoxonase-1 polymorphisms with other gene products implicated in glucose metabolism.