BACKGROUND: In the present study we sought to evaluate the impact of the PPAR-gamma2 Pro12Ala polymorphism on blood lipid levels of primary school children. METHODS: 81 male and 92 female schoolchildren were genotyped. Biochemical, anthropometric, and lifestyle variables were assessed. RESULTS: 14.1% females and 14.8% males were heterozygotes, while the rest of the subjects were homozygotes for the Pro allele. A significant interaction between the PPARgamma-2 gene and gender on blood lipid levels was detected. In particular, Pro/Pro females exhibited higher values of total cholesterol (194 +/- 32 vs 180 +/- 28 mg/dL, P = 0.06) and triglycerides (94 +/- 31 vs 77 +/- 11 mg/dL, P = 0.045) compared to Pro/Ala individuals. The gene-to-gender interaction term was highly significant (P < 0.001). On the other hand, Pro/Pro males showed higher values of HDL cholesterol (47 +/- 8 vs 43 +/- 9 mg/dL, P = 0.001), lower total cholesterol/HDL ratio (4.04 +/- 0.59 vs 4.45 +/- 0.61, P = 0.031), lower values of apoB (59.8 +/- 11.3 vs 66.8 +/- 6.6 mg/dL, P = 0.007) and lower values of apoB/apoA1 ratio (0.41 +/- 0.09 vs 0.48 +/- 0.08, P = 0.019) compared with Pro/Ala. Even after adjusting for body mass index (BMI), total energy intake, total fat intake and saturated fat intake, differences in total cholesterol/high-density lipoprotein (HDL) cholesterol and the apoB/apoA1 ratios remained significant. Regarding females, no differences were observed among genotypes concerning total cholesterol/HDL levels (P for gene-to-gender interaction = 0.001) and the apoB/apoA1 levels (P for gene-to-gender interaction = 0.029). CONCLUSION: We show for the first time a gene-to-gender interaction on total cholesterol/HDL and apoB/apoA1 ratios, in male schoolchildren genotyped for PPAR-gamma2 Pro12Ala.