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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/2483

    Title: Pharmocogenetic study on efficacy of recombinant growth hormone treatment in short stature patients with growth hormone deficiency
    Authors: Wei-Cheng Chen
    Contributors: Department of Biotechnology
    Keywords: growth hormone;growth hormone deficiency;single nucleotide polymorphism
    Date: 2006
    Issue Date: 2009-11-06 14:10:20 (UTC+8)
    Publisher: Asia University
    Abstract: Growth hormone (GH) is the most important one to stimulate human body growth and it is especially significant for children before puberty. Although the factors resulting in slow growth can be divided into the environment factor and the heredity factor, administering growth hormone is the best treatment for different slow growth. In clinical study, the therapy efficacy is significant for the patients with growth hormone deficiency (GHD), one year after treatment with growth hormone. However, their growth altitudes are different. Hence, it is thought to relate to individual hereditary characteristics. Here, we found out the suitable genetic marker related growth adjustment by assaying single nucleotide polymorphism (SNP). The results for GHR condon440 (G/T) revealed a statistically significant difference between GHD patients and normal controls (p<0.05). When the nucleotide change in this site is from G to T, it would lead to a non-synonymous amino acid change from cysteine to phenylalanine. One year after growth hormone treatment, GHD patients with GHR-T/T genotype gained higher average height than G/G and G/T genotypes. In order to realize the mechanism of this polymorphism, growth hormone receptors with G/G or T/T genotype in their condon440 were transfected into CHO-K1 cells. Reporter assays for TK promoter were conducted to compare bioactivity bioactivity of two genotypes. Our data revealed that Cells with T/T genotoype of GHR had higher alkaline phosphatase activity than G/G genotype after luciferase activity was normalized. Futhermore, GH-induced phosphorylation of STAT5 (Tyr694) and p-PKCβII(Ser660)in CHO-K1 cells expressing T/T genotype of GHR was higher than those of G/G genotype. Therefore, it could be concluded that GHR condon440 (G/T) polymorphism is obviously associated to GHD patient’s tall regulation.
    Appears in Collections:[生物科技學系] 博碩士論文

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