| Project/Area Number |
12670728
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
MINAGAWA Masanori (2001) Chiba University, University Hospital, Assistant, 医学部・附属病院, 助手 (50333464)
安田 敏行 (2000) 千葉大学, 医学部, 講師 (00211615)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Tomoyuki Chiba University Hospital, Dept. of Pediatrics, Clinical Fellow, 医学部・附属病院, 医員
KUROKI Haruo Chiba University, Graducate School of Medicine, Assistant, 大学院・医学研究院, 助手 (90292698)
南谷 幹史 千葉大学, 医学部, 医員
皆川 真規 千葉大学, 医学部, 医員
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | PTH / PTHrP receptor / height / growth / gene polymorphism / lower segment length / bone metabolism / DNA methylation / promoter / SOX9 / GH受容体 |
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| Research Abstract |
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.
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