Effects of the interaction between lean tissue mass and estrogen receptor α gene polymorphism on bone mineral density in middle-aged and elderly Japanese

Because both genetic and environmental factors influence bone mass, it is important to examine the effect of gene-environment interactions on bone mineral density (BMD) for the prevention of osteoporosis at an individual level. Estrogen receptor α (ERα) plays an important role in increasing BMD via mechanical strain and muscle mass is a reflection of the forces the muscle applies to the bone. The aim of this study is to investigate the effect of the interaction between lean tissue mass (LTM) and the ERα polymorphisms T → C (PvuII) [dbSNP: rs2234693] and A → G (XbaI) [dbSNP: rs9340799] on BMD in middle-aged and elderly individuals. Subjects were 2209 community-dwelling Japanese men and women, ages 40 to 79 years. ERα polymorphisms in the first intron, T → C and A → G were identified and lumbar spine and femoral neck BMD and LTM were measured by dual-energy X-ray absorptiometry. Both T → C and A → G polymorphisms were divided into two genotype groups (TT vs. TC/CC; AA vs. AG/GG). In postmenopausal women, the effect of LTM on femoral neck BMD was significantly larger for those with the TC/CC genotype than for those with the TT genotype for the T → C polymorphism, and larger for those with the AG/GG genotype than for those with the AA genotype for the A → G polymorphism. This gene–LTM interaction was observed at the femoral neck, but not at the lumbar spine. For men and premenopausal women, no gene–LTM interaction was found. In conclusion, there was an interaction between LTM and the ERα T → C and A → G polymorphisms with respect to their effect on femoral neck BMD in postmenopausal women and those with the TC/CC and AG/GG genotypes had larger effects of LTM than those with TT and AA genotypes.