Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-linked enzyme which appears to protect low-density lipoproteins (LDL) from oxidation. PON1 activity is associated with variation at the PON1 gene locus, specifically the common amino acid polymorphism at codon 192, for which the Q192 allele specifies low activity and the R192 allele specifies high activity. We investigated the association between the PON1 codon 192 polymorphism and fasting concentrations of glucose, lipids, lipoproteins and PON1 activity in 1380 subjects (724 men and 656 women). Several anthropometric and environmental factors were assessed in the present study. The PON1 Q192 allele frequency was 0.70 and 0.68 in men and women, respectively. In women, but not in men, significant associations were found between the PON1 codon 192 genotype and both total and LDL-cholesterol (p=0.004 and p=0.008, respectively), and subgroup analysis indicated that this relationship was predominant in postmenopausal women. Specifically, the Q192 allele was associated with increased total and LDL-cholesterol concentrations. Furthermore, these lipoprotein variables were higher among postmenopausal women with Q192/Q192 and Q192/R192 genotypes than in premenopausal women with the same genotypes (p<0.001). The findings suggest a gender-specific lipoprotein-genotype association with PON1 codon 192 genotypes in this study sample.