Association of a polymorphism of the dopamine receptor D4 gene with bone mineral density in Japanese men.

A -521C-->T polymorphism in the promoter of the dopamine receptor D4 gene (DRD4) has been associated with novelty-seeking behavior in Japanese. Given that the dopaminergic system might also play an important role in bone metabolism, the relation of the -521C-->T polymorphism of DRD4 to bone mineral density (BMD) was examined in 2,228 Japanese subjects (1,123 men; 1,105 women) who were randomly recruited to a population-based, prospective cohort study. BMD at the radius was measured by peripheral quantitative computed tomography, and that for the total body, lumbar spine, right femoral neck, right trochanter, and right Ward's triangle was measured by dual-energy X-ray absorptiometry. Genotype was determined with a fluorescence-based allele-specific DNA primer assay system. For men, BMD for the distal radius, total body, lumbar spine, trochanter, or Ward's triangle was lower in individuals with the CC genotype than in the combined group of TT and TC genotypes or in those with the TT genotype or with the TC genotype. The urinary concentration of deoxypyridinoline was slightly, but significantly, greater in men with the CC genotype than in those with the TT or TC genotypes or with the TT genotype. For women, there were no differences in BMD among -521C-->T genotypes. These results implicate DRD4 as a candidate locus for reduced BMD in Japanese men.