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Study for genetic determinants in height growth and body proportion

身高生长和身体比例的遗传决定因素研究

基本信息

批准号：
12670728
负责人：
MINAGAWA Masanori
金额：
$ 2.18万
依托单位：
CHIBA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670728/
关键词：
PTH PTHrP receptor height growth gene polymorphism lower segment length bone metabolism DNA methylation promoter SOX9 GH受容体

项目摘要

Height growth is genetically determined and approximately 60 % of this process is achieved by endochondral bone formation of long bones. The PTH/PTHrP receptor (PTHR1) mediates the signal of parathyroid hormone-related peptide (PTHrP) which is an important regulator of endochondral bone formation. In functional study AAAG6 polymorphism in P3 promoter of PTHR1 gene have the lowest promoter activity among 3, 5, 6, 7 and 8 times repeat numbers which are found in normal Japanese and Caucasian population. In the female subjects of young adults and junior high school students, the group having AAAG6 polymorphism, which might have low PTHR1 level, was taller than other groups. This promoter polymorphism is one of the factors specifying the individual difference of height growth. The body proportion assessed by the upper / lower segment length ratio (U/L ratio) by means of spina malleolar distance (SMD) was not different between groups with various repeat number of AAAG. Gsα protein mediates the intracellular signal of PTHR1. The mutations in Gsα protein causes pseudohypoparathyroidism type Ia accompanied by short stature. Since the DNA methylation in the regulatory region of the gene may influence the amount of Gsα, we studied the methylation pattern in the 5' regulatory region of Gsα gene in pseudohypoparathyroidism type Ia and type Ib. However, the abnormality in DNA methylation was found only in type Ib, which does not accompany by short stature. In this study, we established the new standard for U/L ratio. This standard is useful when evaluating the children with growth disorders. We examined PTHR1 polymorphism and bone mineral density in the subjects with peak bone mass and found no relationship, however, bone resorption markers were low in AAAG6 group. This may relate the rate of bone mineral loss by aging and warrants further investigation.

身高生长是由基因决定的，该过程约60%是通过长骨的软骨内骨形成实现的。PTH/PTHrP受体（PTHR 1）介导甲状旁腺激素相关肽（PTHrP）的信号，PTHrP是软骨内骨形成的重要调节因子。PTHR 1基因P3启动子区AAAG 6多态性在正常日本人和高加索人中的启动子活性在3、5、6、7和8倍重复数中最低。在青年和初中女生中，AAAG 6多态性组的PTHR 1水平可能较低，其身高高于其他组。这种启动子多态性是决定身高生长个体差异的因素之一。不同AAAG重复次数的组间，用棘踝距离（SMD）的上/下节长度比（U/L比）评估的身体比例没有差异。Gsα蛋白介导PTHR 1的胞内信号。Gsα蛋白的突变导致Ia型假性甲状旁腺功能减退伴身材矮小。由于Gsα基因调控区DNA甲基化可能影响Gsα的表达量，我们研究了Ia型和Ib型假性甲状旁腺功能减退症Gsα基因5'调控区的甲基化模式。然而，DNA甲基化的异常仅在Ib型中发现，其不伴随身材矮小。在本研究中，我们建立了U/L比的新标准。这一标准在评估儿童生长障碍时是有用的。我们检测了PTHR 1基因多态性和骨密度在峰值骨量的受试者中，没有发现相关性，但AAAG 6组的骨吸收标志物较低。这可能与骨矿物质损失率老化和值得进一步调查。