To investigate the relationship between parental history of myocardial infarction (MI), lipid traits and gene polymorphisms involved in lipid metabolism, we examined Dutch men and women, who were selected from a large population-based study. Subjects whose father (n=112), mother (n=115) or both parents (n=115) suffered from a premature MI presented with significantly higher apolipoprotein B (apo B) levels than subjects without a parental history (n=114). Genetic analyses revealed that the apo E4 isoform and the D9N mutation of lipoprotein lipase (LPL) were more frequent among subjects with a parental history (P< or =0.05). A similar trend was found for the LPL N291S mutation. In contrast, the LPL S447X mutation and polymorphisms at the cholesteryl ester transfer protein (TaqIB) and apo CIII (SstI) loci proved to be noninformative. Body mass index and lifestyle could not explain differences in apo B levels between parental history groups. In contrast, the apo E polymorphism and the LPL D9N mutation accounted for some, but not all, of the higher apo B levels in subjects with a parental history. Therefore, other genetic or lifestyle-related factors must be responsible for the increased levels of apo B in individuals with a family history of myocardial infarction.