Evidence suggests the existence of a close relation between lipid metabolism and bone remodeling. We hypothesized that polymorphisms of genes that play a role in lipid metabolism, such as those for forkhead box C2 (FOXC2) and perilipin (PLIN), might affect bone mineral density (BMD). We thus examined the possible relationships between a -512C→T polymorphism of FOXC2 and a 1243C→T polymorphism of PLIN to BMD in communitydwelling Japanese women and men. The subjects (1129 men, 1114 women for

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... ; 1122 men, 1112 women for PLIN) were aged 40 to 79 years and were randomly recruited to a population-based prospective cohort study of aging and agerelated diseases in Japan. Genotypes for FOXC2 and PLIN were determined with a fluorescence-based allele-specific DNA primer assay system. The -512C→T polymorphism of FOXC2 was associated with BMD for the distal and proximal radius in men and in premenopausal women as well as with BMD for the distal radius and total body in postmenopausal women, with the T allele being related to reduced BMD. The 1243C→T polymorphism of PLIN was associated with BMD for the total body, lumbar spine, femoral neck, and trochanter in men, with the C allele being related to reduced BMD. This polymorphism of PLIN was not associated with BMD in all women. These results suggest that FOXC2 is a susceptibility locus for reduced BMD in Japanese men and women, and that PLIN constitutes such a locus in Japanese men.