ABSTRACT: Background: The apolipoprotein E (APOE) gene plays a pivotal role in cholesterol metabolism. Since the discovery of the APOE*2 and APOE*4 as the major susceptibility alleles for several diseases including dyslipidemia, atherosclerosis, coronary heart disease, late-onset and early Alzheimer’s disease, the APOE genotype might be considered as a potential predictive factor for both epidemiological research and diagnosis. Aim: The aim of this study is to report on the polymorphism of the APOE gene in the ‘‘Paisa’’ population from northwest Colombia (Antioquia) to obtain a population baseline of the existing variation in this locus. Method: One thousand and one healthy voluntaries were genotyped for the APOE polymorphism using polymerase chain reaction–restriction fragment length polymorphism technique. Results: The APOE*3/*3 genotype presented the highest frequency (66.33%) and the APOE*4/*4 had the lowest frequency (1.89%). Genotype frequencies comply with Hardy–Weinberg expectations. Allele frequencies obtained for APOE*2, APOE*3 and APOE*4 were 0.075 ± 0.005 (95% CI ¼ 0.063–0.086), 0.814 ± 0.009 (0.797–0.831) and 0.111 ± 0.007 (0.098–0.125), respectively. Conclusion: Although globally the high-to-low APOE frequency follows the E*34E*44E*2 trend, the present APOE frequency data is in disagreement with some reports from SouthAmerican countries.COL0006723COL0010744