Genetic variants of the microsomal triglyceride transfer protein (MTP) have been associated with the serum concentration of low density lipoprotein-cholesterol, predisposition to coronary heart disease, or longevity. The relation of a -493Gright curved arrow T polymorphism in the promoter of MTP to blood pressure was examined in a population-based study. The subjects (1124 men, 1108 women) were aged 40-79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases in Japan. Blood pressure was measured at least twice with subjects in the sitting position. The serum lipid profile was determined after the subjects had fasted overnight. The -493Gright curved arrow T genotype of MTP was determined with a fluorescence-based allele-specific DNA primer assay system. There was no difference in the serum concentrations of total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, or triglycerides among MTP genotypes for men or for women. Systolic or diastolic blood pressure was not related to the -493Gright curved arrow T polymorphism in men. For women, however, systolic and diastolic blood pressures were significantly related to MTP genotype, with the T allele of the polymorphism being associated with low blood pressure. The relation between MTP genotype and the prevalence of hypertension was almost significant (P=0.055) for all women. Although MTP genotype was not associated with the prevalence of hypertension in premenopausal women, the relation between these parameters was significant (P=0.040) in postmenopausal women, with the TT genotype protecting against this condition. These results suggest that MTP genotype is a determinant of blood pressure in Japanese women.