Association of a Trp16Ser variation in the gonadotropin releasing hormone signal peptide with bone mineral density, revealed by SNP-dependent PCR typing
Association of a Trp16Ser variation in the gonadotropin releasing hormone signal peptide with bone mineral density, revealed by SNP-dependent PCR typing
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DOI：
10.1016/s8756-3282(02)00949-3
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发表时间：
2003-02-01
期刊：
影响因子：
4.1
通讯作者：
Orimo, H
中科院分区：
文献类型：
--
作者：
Iwasaki, H;Emi, M;Orimo, H
骨质疏松症被认为是多种环境和遗传因素相互作用的结果，包括调节骨矿物质密度（BMD）的因素。在这些因素中，足够的雌激素对于达到峰值骨量以及绝经后维持骨骼稳态是必不可少的。来自下丘脑的促性腺激素释放激素（GnRH）是下丘脑-垂体-性腺反馈系统中的主要决定因素。在对384名绝经后日本妇女的遗传学研究中，我们发现BMD与位于GnRH信号肽内的氨基酸变异（Trp 16 Ser）之间存在显著相关性（r = 0.143，P = 0.005）。这些结果是通过使用新开发的SNP依赖性PCR方法对所有受试者进行基因分型来实现的。这种自动化、高通量和廉价的程序适用于大量样品的分型。16 Ser/Ser纯合子BMD最低，16 Trp/Trp纯合子BMD最高，杂合子BMD居中。一项包括125名骨质疏松症患者和92名健康对照的病例对照研究显示，16 Ser GnRH等位基因的存在与骨质疏松症的患病状态之间存在显著相关性（χ 2 = 4.74，P = 0.041）。提示GnRH信号肽的变化可能是绝经后骨质疏松的重要危险因素。(C)2003 Elsevier Science（美国）。All rights reserved.
Osteoporosis is believed to result from interplay among multiple environmental and genetic determinants, including factors that regulate bone mineral density (BMD). Among those factors, adequate estrogen is essential for achievement of peak bone mass as well as for postmenopausal maintenance of skeletal homeostasis. Gonadotropin-releasing hormone (GnRH) from the hypothalamus is the primary determinant in the hypothalamic-pituitary-gonadal feedback system. In genetic studies of 384 postmenopausal Japanese women, we found a significant association between BMD and an amino acid variation (Trp16Ser) located within the signal peptide of GnRH (r = 0.143, P = 0.005). These results were achieved by genotyping all subjects using a newly developed SNP-dependent PCR method. This automated, high-throughput, and inexpensive procedure is suitable for typing large numbers of samples. BMD was lowest among 16Ser/Ser homozygotes, highest among 16Trp/Trp homozygotes, and intermediate among heterozygotes. A case-control study involving 125 osteoporosis patients and 92 healthy controls revealed a significant association between the presence of a 16Ser GnRH allele and affected status (chi(2) = 4.74, P = 0.041). The results suggested that variation of the GnRH signal peptide may be an important risk factor for postmenopausal osteoporosis. (C) 2003 Elsevier Science (USA). All rights reserved.