Yamada Y, Miyauchi A, Takagi Y, Tanaka M, Mizuno M, Harada A
Department of Gene Therapy, Gifu International Institute of Biotechnology, Mitake, Japan.
J Mol Med (Berl). 2001 Apr;79(2-3):149-56. doi: 10.1007/s001090100190.
Transforming growth factor-beta1 is an important local regulator of bone metabolism, acting downstream of estrogen and cooperatively with vitamin D. The possible association of a C 509-->T polymorphism in the promoter region of the transforming growth factor-beta1 gene, alone or in combination with a T869-->C (Leu10-->Pro) polymorphism, with bone mineral density and genetic susceptibility to osteoporosis was investigated in 625 postmenopausal Japanese women. The frequencies of the CC, CT, and TT genotypes of the C-509-->T polymorphism in the study population were 24%, 49%, and 27%, respectively. A significant association of C-509-->T genotype with bone mineral density was detected: lumbar spine (L2-L4) and total body bone mineral density values were 7% and 5% lower, respectively, in individuals with the TT genotype than in those with the CT or CC genotype. The serum concentration of transforming growth factor-beta1 did not vary with C-509-->T genotype. Multivariable logistic regression analysis, with adjustment for age, height, body weight, time since menopause, smoking status, body fat mass, and lean mass, revealed a significantly higher frequency of the TT genotype of the C-509-->T polymorphism in 286 individuals with osteoporosis than in 170 normal controls. Analysis of combined C-509-->T and T869-->C genotypes showed that L2-L4 bone mineral density decreases and the prevalence of osteoporosis increases with the number of T alleles. These results suggest that the C-509-->T polymorphism, alone or in combination with the T869-->C polymorphism, of the transforming growth factor-beta1 gene is a genetic determinant of bone mass, and that the number of T alleles in the combined genotype is a risk factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese women.
转化生长因子-β1是骨代谢的重要局部调节因子，作用于雌激素下游并与维生素D协同发挥作用。本研究在625名绝经后日本女性中，调查了转化生长因子-β1基因启动子区域C509→T多态性单独或与T869→C（Leu10→Pro）多态性联合，与骨密度及骨质疏松遗传易感性之间的可能关联。研究人群中C-509→T多态性的CC、CT和TT基因型频率分别为24%、49%和27%。检测到C-509→T基因型与骨密度存在显著关联：TT基因型个体的腰椎（L2-L4）和全身骨密度值分别比CT或CC基因型个体低7%和5%。转化生长因子-β1的血清浓度未随C-509→T基因型而变化。在对年龄、身高、体重、绝经时间、吸烟状况、体脂量和瘦体重进行校正的多变量逻辑回归分析中，286例骨质疏松患者中C-509→T多态性的TT基因型频率显著高于170例正常对照。对C-509→T和T869→C联合基因型的分析表明，L2-L4骨密度随T等位基因数量的增加而降低，骨质疏松患病率升高。这些结果表明，转化生长因子-β1基因的C-509→T多态性单独或与T869→C多态性联合，是骨量的遗传决定因素，联合基因型中T等位基因数量是绝经后日本女性骨质疏松遗传易感性的危险因素。
