Association of a Polymorphism of the Transforming Growth Factor‐β1 Gene with Genetic Susceptibility to Osteoporosis in Postmenopausal Japanese Women
Association of a Polymorphism of the Transforming Growth Factor‐β1 Gene with Genetic Susceptibility to Osteoporosis in Postmenopausal Japanese Women
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DOI：
10.1359/jbmr.1998.13.10.1569
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发表时间：
1998-10
影响因子：
6.2
通讯作者：
Yoshiji Yamada;A. Miyauchi;Junki Goto;Y. Takagi;H. Okuizumi;M. Kanematsu;M. Hase;H. Takai;A. Harada;K. Ikeda
中科院分区：
文献类型：
--
作者：
Yoshiji Yamada;A. Miyauchi;Junki Goto;Y. Takagi;H. Okuizumi;M. Kanematsu;M. Hase;H. Takai;A. Harada;K. Ikeda
转化生长因子-β(转化生长因子-β)在骨组织中含量丰富，是骨代谢的重要调节因子。转化生长因子-→-1基因信号序列中29位核苷酸的T-βC突变导致第10位氨基酸的亮氨酸→-Pro突变。在两个人群中均检测到转化生长因子-β-1基因与骨量显著相关；CC基因携带者腰椎骨密度高于TT或TC基因携带者。CC基因携带者的椎体骨折发生率显著低于TC或TT基因携带者。多变量Logistic回归分析显示，骨质疏松症患者的T等位基因频率显著高于对照组。在骨质疏松组、骨质疏松症组和健康对照组中，CC基因携带者的血清转化生长因子-β-1水平显著高于年龄匹配的TC和TT基因携带者。这些结果提示，转化生长因子-β-1基因T/C多态性是骨量的遗传决定因素之一，T等位基因是日本绝经后妇女骨质疏松遗传易感性的独立危险因素。因此，对转化生长因子-β-1基因的分析可能有助于骨质疏松症的预防和治疗。
Transforming growth factor‐β (TGF‐β) is both abundant in bone and an important regulator of bone metabolism. A T→C transition at nucleotide 29 in the signal sequence region of the TGF‐β1 gene results in a Leu→Pro substitution at amino acid position 10. The possible association of this polymorphism with bone mass and the prevalence of osteoporosis has now been investigated in a total of 287 postmenopausal women from two regions (Obu City, Aichi Prefecture, and Sanda City, Hyogo Prefecture) of Japan. A significant association of TGF‐β1 genotype with bone mass was detected in both populations; bone mineral density (BMD) at the lumbar spine was greater in individuals with the CC genotype than in those with the TT or TC genotype. The frequency of vertebral fractures was significantly lower in individuals with the CC genotype than in those with the TC or TT genotypes. For each region, multivariable logistic regression analysis revealed that the frequency of the T allele was significantly higher in subjects with osteoporosis than in controls. Also, the serum concentration of TGF‐β1 in individuals with the CC genotype was significantly higher than that in age‐matched subjects with the TC or TT genotype in osteoporotic or osteopenic as well as healthy control groups. These results suggest that the T/C polymorphism of the TGF‐β1 gene is one of the genetic determinants of bone mass and that the T allele is an independent risk factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese women. Thus, analysis of the TGF‐β1 genotype may be useful in the prevention and management of osteoporosis.