Yamada Yoshiji, Ando Fujiko, Niino Naoakira, Shimokata Hiroshi
Department of Gene Therapy, Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan.
Mol Genet Metab. 2003 Nov;80(3):344-9. doi: 10.1016/S1096-7192(03)00125-2.
Given that osteoprotegerin plays an important role in bone remodeling, the osteoprotegerin gene may be a candidate locus for susceptibility to osteoporosis. The relation of polymorphisms in the promoter of the osteoprotegerin gene to bone mineral density (BMD) was examined in a Japanese population-based prospective cohort study with randomly recruited subjects (1095 women and 1125 men for the 950T --> C polymorphism, 1094 women and 1127 men for the 245T --> G polymorphism). 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. Genotypes were determined with a fluorescence-based allele-specific DNA primer assay system. Among 950T --> C genotypes, BMD for the proximal radius was lower in premenopausal women with the CC genotype than in those with the TT or TC genotype; the difference in BMD between the two groups was 3.9% (P=0.0075). Among 245T --> G genotypes, BMD for the radius, total body, femoral neck, trochanter, and Ward's triangle was lower in postmenopausal women with the GG genotype than in those with the TT or TG genotype, the TT genotype, or the TG genotype; the differences in BMD between the GG genotype and the TT or TG genotype were 19.8% for the distal radius (P=0.0015), 13.1% for the proximal radius (P=0.0095), 11.2% for the total body (P=0.0013), 12.9% for the femoral neck (P=0.0067), 18.7% for the trochanter (P=0.0008), and 27.1% for Ward's triangle (P=0.0038). BMD was not associated with the 950T --> C or 245T --> G genotypes in men. The present results implicate the osteoprotegerin gene as a susceptibility locus for reduced BMD in Japanese women.
鉴于骨保护素在骨重塑中起重要作用，骨保护素基因可能是骨质疏松易感性的候选基因座。在一项基于日本人群的前瞻性队列研究中，对随机招募的受试者（950T→C多态性研究中1095名女性和1125名男性，245T→G多态性研究中1094名女性和1127名男性），研究了骨保护素基因启动子多态性与骨密度（BMD）的关系。桡骨骨密度通过外周定量计算机断层扫描测量，全身、腰椎、右股骨颈、右转子和右Ward三角区的骨密度通过双能X线吸收法测量。采用基于荧光的等位基因特异性DNA引物分析系统确定基因型。在950T→C基因型中，CC基因型的绝经前女性近端桡骨骨密度低于TT或TC基因型的女性；两组骨密度差异为3.9%（P=0.0075）。在245T→G基因型中，GG基因型的绝经后女性桡骨、全身、股骨颈、转子和Ward三角区的骨密度低于TT或TG基因型、TT基因型或TG基因型的女性；GG基因型与TT或TG基因型之间的骨密度差异在远端桡骨为19.8%（P=0.0015），近端桡骨为13.1%（P=0.0095），全身为11.2%（P=0.0013），股骨颈为12.9%（P=0.0067），转子为18.7%（P=0.0008），Ward三角区为27.1%（P=0.0038）。男性的骨密度与950T→C或245T→G基因型无关。目前结果表明骨保护素基因是日本女性骨密度降低的易感基因座。
