Kitamura Itsuko, Ando Fujiko, Koda Michiko, Okura Tomohiro, Shimokata Hiroshi
Department of Epidemiology, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka-cho, Obu, Aichi, 474-8522, Japan.
Bone. 2007 Jun;40(6):1623-9. doi: 10.1016/j.bone.2007.02.016. Epub 2007 Feb 23.
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 alpha (ER alpha) 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 ER alpha 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. ER alpha 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 ER alpha 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.
由于遗传和环境因素均会影响骨量，因此在个体层面上研究基因 - 环境相互作用对骨矿物质密度（BMD）的影响对于预防骨质疏松症很重要。雌激素受体α（ERα）通过机械应变在增加骨密度方面发挥重要作用，而肌肉量反映了肌肉施加于骨骼的力量。本研究的目的是调查瘦组织质量（LTM）与ERα基因多态性T→C（PvuII）[dbSNP：rs2234693]和A→G（XbaI）[dbSNP：rs9340799]之间的相互作用对中老年个体骨密度的影响。研究对象为2209名年龄在40至79岁之间的日本社区居民男女。确定了第一个内含子中的ERα基因多态性T→C和A→G，并通过双能X线吸收法测量腰椎和股骨颈骨密度以及瘦组织质量。T→C和A→G多态性均分为两个基因型组（TT与TC/CC；AA与AG/GG）。在绝经后女性中，对于T→C多态性，TC/CC基因型者的LTM对股骨颈骨密度的影响显著大于TT基因型者；对于A→G多态性，AG/GG基因型者的LTM对股骨颈骨密度的影响显著大于AA基因型者。这种基因 - LTM相互作用在股骨颈处观察到，但在腰椎处未观察到。对于男性和绝经前女性，则未发现基因 - LTM相互作用。总之，LTM与ERα基因多态性T→C和A→G之间存在相互作用，对绝经后女性股骨颈骨密度有影响，且TC/CC和AG/GG基因型者的LTM影响大于TT和AA基因型者。
